angiotensinogen and Coronary-Artery-Disease

It is thought that genetic factors may play an important role in the development of coronary artery disease (CAD). Several studies report that AGT polymorphism is implicated in CAD susceptibility, but these results contradict those of the other studies with the associations being unclear in the Eastern Asian population. Therefore, meta-analysis was performed to evaluate this relationship.. Publication databases were used to search for eligible relevant studies and valid data were extracted from studies meeting the inclusion criteria. Subsequently, odds ratios (ORs) with 95 % confidence intervals (CIs), were used to assess the strength of the association between AGT polymorphism and CAD risk.. Seven eligible studies published only in English were included in the present meta-analysis. In the Eastern Asian population, CAD susceptibility was shown to be related to AGT M235T under the heterozygote model (OR = 0.19). Stratified analysis indicated there was a significant relationship between AGT M235T and CAD risk in China under allelic (OR = 1.34), dominant (OR = 1.43), and heterozygote (OR = 1.62) models. The results showed that the T174M polymorphism was significantly associated with CAD risk in recessive (OR = 2.28) and homozygote (OR = 2.37) models in the Eastern Asian population.. In the Eastern Asian population, especially the Chinese, the M235T of AGT is associated with CAD susceptibility. The T174M polymorphisms were associated with CAD risk in the Eastern Asian population.

Topics: Angiotensinogen; Asian People; Coronary Artery Disease; Genetic Predisposition to Disease; Humans; Polymorphism, Genetic; Risk Factors

To explore the association between the variant M235T locus of angiotensinogen (AGT) gene, 584C/T locus of Endothelial lipase (EL) gene, and coronary artery disease (CAD) by meta-analysis.. The case-control studies on the association between AGT/EL gene polymorphism and CAD were collected through searching PubMed, Excerpta Medica Database (EMBASE), Web of Science, China National Knowledge Infrastructure (CNKI), and Wanfang databases up to 1 March 2020. Stata 15.0 software was used for analysis.. A total of 29 articles met the inclusion criteria. After analyzing, it was found that the M235T polymorphism of AGT gene was associated with the occurrence of CAD. In the allele model (T vs. M), OR = 1.38 (P

Topics: Alleles; Angiotensinogen; Asian People; Case-Control Studies; Coronary Artery Disease; Genetic Predisposition to Disease; Heterozygote; Humans; Lipase; Models, Genetic; Polymorphism, Single Nucleotide; Risk Factors; White People

The angiotensinogen (AGT) gene M235T polymorphism has been suggested to be linked with susceptibility to coronary artery disease (CAD). In the present study, a meta-analysis was performed to assess the correlation between the M235T polymorphism and CAD. Nine studies with a total of 2281 subjects were selected for inclusion in the analysis. The references were retrieved via PubMed, China National Knowledge Infrastructure, Wanfang and VIP database (1995.1-2012.1). The analyses were performed using STATA 10.0 software. Odds ratios (OR) with 95% confidence intervals (CIs) were assessed after the collected data were pooled for analysis. A significant association was detected between M235T gene polymorphism and CAD in the population studied. The estimates (OR) of CAD risk were calculated in a homozygote comparison (OR=1.54; 95% CI, 1.09-2.16), a heterozygote comparison (OR=1.30; 95% CI, 1.07-1.58), a dominant model (OR=0.72; 95% CI, 0.55-0.94) and a recessive model (OR=1.37; 95% CI, 0.98-1.91). The current meta-analysis suggests that the M235T polymorphism is associated to an increased risk of CAD.

Topics: Angiotensinogen; Coronary Artery Disease; Databases, Factual; Heterozygote; Homozygote; Humans; Odds Ratio; Polymorphism, Single Nucleotide; Risk Factors

Several trials demonstrated that angiotensin-converting enzyme inhibitors reduce the incidence of cardiovascular events during long-term follow-up in high-risk and low-risk patients. Clinical treatment guidelines propose that angiotensin-converting enzyme inhibitors should be considered in the routine secondary prevention in the broad group of coronary artery disease patients. This review discusses several approaches to guide angiotensin-converting enzyme-inhibition therapy to more specific groups of patients that are most likely to benefit.. The beneficial effect of angiotensin-converting enzyme inhibition has been shown to be consistent across subgroups in stable coronary artery disease. Still, large interindividual variability in blood pressure response is well documented. It should also be realized that the absolute treatment effects are modest. The efficiency and cost-effectiveness of this prolonged prophylactic treatment would be significantly enhanced if those patients can be distinguished who benefit most. Recently, it was suggested that markers of an activated renin-angiotensin-aldosterone system might be used to guide angiotensin-converting enzyme-inhibition therapy.. At the start of treatment, clinical characteristics are not sufficient to distinguish between patients who will and will not benefit from angiotensin-converting enzyme inhibitors. Although pharmacogenetic research in coronary artery disease is still in a premature stage, it may be expected to provide a useful tool in optimizing and individualizing the management of angiotensin-converting enzyme-inhibitor therapy in coronary artery disease patients.

Topics: Angiotensin-Converting Enzyme Inhibitors; Angiotensinogen; Coronary Artery Disease; Humans; Patient Selection; Peptidyl-Dipeptidase A; Pharmacogenetics

Angiotensinogen (AGT) represents a key component of the renin-angiotensin-aldosterone system (RAAS). Polymorphisms in the 3' untranslated region (3'UTR) of the AGT gene may alter miRNA binding and cause disbalance in the RAAS. Within this study, we evaluated the possible association of AGT +11525C/A (rs7079) with the clinical characteristics of patients with coronary artery diseases (CAD). Selective coronarography was performed in 652 consecutive CAD patients. Clinical characteristics of the patients, together with peripheral blood samples for DNA isolation, were collected. The genotyping of rs7079 polymorphism was performed with TaqMan

Topics: 3' Untranslated Regions; Angiotensinogen; Binding Sites; Coronary Artery Disease; Humans; MicroRNAs; Polymorphism, Genetic

Genetic factors can influence the risk of coronary artery disease (CAD) and the survival of patients. Our previous research led to the identification of genetic variants predisposing to CAD in the Polish population. Since many of them affect the clinical phenotype of the disease, the aim of this study was searching for genetic factors potentially influencing survival in patients with CAD. The study included 276 patients hospitalized due to coronary artery disease. The database of medical history and genotypic results of 29 polymorphisms were used. The endpoint was defined as death from cardiovascular causes. Survival was defined as the period from angiographic confirmation of CAD to death from cardiovascular causes. Three of all the analyzed genes were associated with survival. In the case of the

Topics: Alleles; Angiotensinogen; ATP Binding Cassette Transporter 1; Coronary Artery Disease; Disease Susceptibility; Genotype; Humans; NADPH Oxidases; Polymorphism, Genetic; Prospective Studies

This study investigated the renin-angiotensin-aldosterone system (RAAS) gene polymorphisms as possible genetic risk factors for the restenosis development in patients with drug-eluting stents. 113 participants had coronary artery disease and underwent stenting. The control group consisted of 62 individuals with intact coronary arteries. Patients were divided into two groups: with in-stent restenosis (ISR) and without it. The patients with ISR were classified into subgroups by the terms of the restenosis development and age. Real-time PCR and Restriction Fragment Length Polymorphism-PCR were used to genotype the study participants for RAAS gene polymorphisms. We found that the development of restenosis is generally associated with the minor A allele for renin (REN) rs2368564 and the major TT genotype for angiotensinogen (AGT) rs699. The heterozygous genotype for AGT rs4762 acts as a protective marker. A minor A allele for angiotensin II type 2 receptor (AGTR2) rs1403543 is associated with a risk of restenosis in people under 65 years old. Among patients with the early ISR, heterozygotes for angiotensin II type 1 receptor (AGTR1) rs5186 are more frequent, as well as A allele carriers for AGTR2 rs1403543. A minor homozygous genotype for REN rs41317140 and heterozygous genotype for aldosterone synthase (CYP11B2) rs1799998 are predisposed to the late restenosis. Thus, to choose the effective treatment tactics for patients with coronary artery disease, it is necessary to genotype patients for the RAAS polymorphisms, which, along with age and clinical characteristics, will allow a comprehensive assessment of the risk of the restenosis development after stenting.

Topics: Aged; Angiotensinogen; Coronary Artery Disease; Coronary Restenosis; Cytochrome P-450 CYP11B2; Drug-Eluting Stents; Female; Genetic Predisposition to Disease; Humans; Male; Middle Aged; Polymorphism, Restriction Fragment Length; Polymorphism, Single Nucleotide; Real-Time Polymerase Chain Reaction; Receptor, Angiotensin, Type 1; Receptor, Angiotensin, Type 2; Renin; Renin-Angiotensin System

To investigate the relationship between angiotensin (. Polymerase chain reaction was performed to determine. The

Topics: Angiotensinogen; Angiotensins; Asian People; China; Coronary Artery Disease; Gene Frequency; Genetic Predisposition to Disease; Genotype; Humans; Non-alcoholic Fatty Liver Disease; Polymorphism, Genetic; Polymorphism, Single Nucleotide; Risk Factors

Renin-angiotensin-aldosterone system (RAAS) has an important role in atherosclerosis. We investigated the effects of six RAAS gene polymorphisms on myocardial perfusion.. We examined 810 patients with known or suspected coronary artery disease (CAD) using stress-rest myocardial single-photon emission computed tomography. Summed stress score (SSS), summed rest score (SRS), summed difference score (SDS), transient ischemic dilation (TID), and lung/heart ratio (LHR) were recorded. The following gene polymorphisms were investigated: angiotensin-converting enzyme (ACE) insertion/deletion (I/D), angiotensinogen (AGT) M235T and T174M, angiotensin II type 1 receptor (AT1R) A1166C, renin (REN) C5312T, and angiotensin II type 2 receptor (AT2R) C3123A. The heterozygotes or homozygotes on ACE D allele were 7.54 times more likely to have abnormal SSS, while the AGT (T174M) heterozygotes were 5.19 times more likely to have abnormal SSS. The homozygotes of ACE D had significantly higher values on TID and LHR, while the AGT (T174M) heterozygotes had higher values on TID. The AT1R heterozygotes had greater odds for having SSS ≥ 3. The patients carried AT1R homozygosity of C allele had significantly higher values on TID, while heterozygotes of AT1R had significantly higher values on LHR.. Among the polymorphisms investigated, ACE D allele had the strongest association with abnormal myocardial perfusion.

Topics: Adult; Aged; Aged, 80 and over; Angiotensinogen; Coronary Artery Disease; Coronary Circulation; Female; Humans; Male; Middle Aged; Myocardial Perfusion Imaging; Peptidyl-Dipeptidase A; Polymorphism, Genetic; Receptors, Angiotensin; Renin; Renin-Angiotensin System; Tomography, Emission-Computed, Single-Photon

To assess the association of gene polymorphisms of angiotensinogen (AGT), the key factor in rennin-angiotensin-aldosterone system (RAAS), with high-sensitivity C-reactive protein (hs-CRP) and coronary artery disease (CAD).. The current study recruited the patients who were hospitalized and assessed by coronary angiography for suspected CAD. The patients with documented CAD served as CAD group (n = 492) while the patients without documented CAD (n = 87) served as control group. We compared laboratory data and CAD risk factors between the two groups. Furthermore, we analyzed the association of AGT M235T, G217A, G152A, G-6A, A-20C genotypes with coronary artery stenosis and in-stent restenosis.. There were significantly differences between two patient groups in sex, smoking history, diabetes mellitus, carotid atherosclerosis, lower limb arteriosclerosis, hs-CRP, blood glucose, and the level of high-density lipoprotein (HDL; P < 0.05). In CAD group, hs-CRP levels increased with increasing number of coronary artery branches (1, 2, or ≥3; P < 0.01), and Gensini integral was positively correlated with hs-CRP levels (r = 0.361, P < 0.01). Frequencies of genotype and allele distribution in individual angiotensinogen loci (M235T, G217A, G152A, G-6A, A-20C) did not differ in two patient groups. Following stratification of patients according to hs-CRP levels (<1 mg/L, 1-3 mg/L, and >3 mg/L), the distribution frequency of allele M235T was statistically different among the groups (P < 0.05).. In CAD patients, M235T among several AGT gene polymorphisms is associated with elevated hs-CRP levels with AGT C allele as the significant factor for patients with hs-CRP level of more than 1 mg/L.

Topics: Aged; Angiotensinogen; Asian People; C-Reactive Protein; Case-Control Studies; Coronary Angiography; Coronary Artery Disease; Female; Gene Frequency; Haplotypes; Humans; Male; Middle Aged; Polymorphism, Genetic; Prospective Studies

The rennin-angiotensin-aldosterone system (RAAS) is a critical pathway in regulating blood pressure and salt/water homeostasis, possessing an intimate relationship with the development of systemic artery hypertension (SAH). Once hypertension is considered a risk factor for coronary artery disease (CAD), the RAAS is also related to this pathology. This investigation aimed to analyse if the frequencies of AGT M235T (rs699) and ACE I/D (rs4646994) polymorphisms are associated with CAD and SAH in African-Brazilians and Caucasian-Brazilians. In this study we analysed 714 subjects who underwent coronary angiography to detect obstructive lesions and CAD, as well as blood pressure measurement and SAH, grouped according to ethnicity: 266 African-Brazilians and 448 Caucasian-Brazilians. Among CAD and SAH cases and controls, the genotype and allele frequencies of ACE I/D polymorphism were similar in both ethnic groups. The AGT 235TT genotype and 235T allele frequencies were higher in SAH cases (32%, 54.7%) versus controls in Caucasian-Brazilians (19.8%, 46.4%; P = 0.038, P = 0.031, respectively). The AGT 235TT (OR = 1.8; P = 0.028) demonstrated to be an independent factor risk in a multivariate logistic regression increasing SAH risk in Caucasians but not in African-Brazilians. In summary, AGT M235T polymorphism was associated with SAH risk in Caucasian-Brazilians, and no association was detected with CAD. No association was also observed in ACE I/D polymorphism either in CAD or SAH in African-Brazilians and Caucasian-Brazilians.

Topics: Adult; Angiotensinogen; Black People; Brazil; Case-Control Studies; Coronary Artery Disease; Female; Humans; Hypertension; Male; Middle Aged; Peptidyl-Dipeptidase A; Polymorphism, Genetic; White People

The renin-angiotensin-aldosterone system may influence in-stent restenosis (ISR) via angiotensin II, which stimulates the production of growth factors for smooth muscle cells. The aim of this work is to assess the influence of the rs1799752 polymorphism of the angiotensin-converting enzyme (ACE) gene and the rs699 polymorphism of the angiotensinogen (AGT) gene on the ISR in Polish patients with stable coronary artery disease (SCAD) who underwent stent implantation.. Two hundred and sixty-five patients with SCAD were included in the study. All patients underwent stent implantation upon admission to the hospital and had subsequent coronary angiography performed. The patients were divided into two groups - those with significant ISR (n=53) and those without ISR (n=212). The ACE polymorphism was assessed using the classical PCR method and the AGT polymorphism was determined using the TaqMan method for SNP genotyping.. No difference in the frequency of angiographically significant ISR occurrence associated with the different ACE and AGT gene polymorphisms was observed. In a multivariable analysis, after correction for clinical variables, the relationship between the ACE and AGT genotypes within the scope of the analyzed polymorphisms and the process of restenosis was not found using a dominant, recessive and log-additive model. Late lumen loss was also independent of the genotypes of the polymorphisms before and after correction with angiographic variables.. The rs1799752 polymorphism and the rs699 polymorphism had no relationship with the occurrence of angiographically significant ISR and late lumen loss in a group of Polish patients who underwent metal stent implantation.

Topics: Aged; Angiotensinogen; Cohort Studies; Coronary Angiography; Coronary Artery Disease; Coronary Restenosis; Female; Genetic Predisposition to Disease; Humans; Male; Middle Aged; Peptidyl-Dipeptidase A; Poland; Polymorphism, Single Nucleotide; Stents

The aim of the present study was to evaluate the role of AGT and REN gene polymorphisms as susceptibility markers for coronary artery disease (CAD) and/or restenosis after coronary stent placement in a group of Mexican patients. Five polymorphisms of the AGT (rs699, rs4762, rs5051, rs5049, rs5046) and two of the REN (rs5707, rs5705) genes were analyzed by 5' exonuclease TaqMan genotyping assays in 240 patients with CAD who underwent coronary artery stenting (76 with restenosis and 164 without restenosis). A group of 610 individuals without clinical and familial antecedents of cardiovascular diseases were included as controls. The results showed that the distribution of AGT and REN polymorphisms were similar in patients with and without restenosis. However, when the whole group of patients (with and without restenosis) was compared to healthy controls, under co-dominant, dominant, heterozygous and additive models, the REN A4280C (rs5705) polymorphism was associated with increased risk of CAD (OR=1.76, PCo-dom=0.006, OR=1.81, PDom=0.001, OR=1.75, PHet=0.003 and OR=1.59, PAdd=0.003, respectively). All models were adjusted for age, gender, diabetes, dyslipidemia, hypertension and smoking habit. The TC haplotype of the REN gene was associated with increased risk of CAD (OR=1.53, P=0.014). The data suggest that the REN C4280A (rs5705) polymorphism plays an important role in the risk of developing CAD with the highest risk for C allele, but do not support its role as a risk factor for developing restenosis after coronary stenting.

Topics: Aged; Alleles; Angiotensinogen; Case-Control Studies; Computational Biology; Coronary Artery Disease; Coronary Restenosis; Female; Gene Frequency; Genetic Markers; Genetic Predisposition to Disease; Genotyping Techniques; Haplotypes; Heterozygote; Humans; Linkage Disequilibrium; Logistic Models; Male; Mexico; Middle Aged; Polymorphism, Single Nucleotide; Renin; Risk Factors; Stents

To investigate intercellular adhesion molecule-1 (ICAM1) and angiotensinogen (AGT) gene polymorphisms, as related to atherosclerosis and endothelial dysfunction, in coronary slow flow (CSF).. The participants in this study were 48 patients with CSF and 67 patients with normal coronary flow as controls. The K469E polymorphism of ICAM1 (rs5498) and the T207M polymorphism of AGT (rs4762) were determined using the polymerase chain reaction amplification method.. Baseline demographic parameters were similar in both groups. The mean thrombolysis in myocardial infarction frame count was significantly higher in patients with CSF (23.8 ± 5.1) compared to the controls (13.3 ± 2.6, p < 0.001). A significant association was found between the ICAM1 K allele and CSF (OR: 1.96, 95% CI: 1.15-3.35, p = 0.013). There was no difference in the frequency of AGT T207M genotypes in the patients with CSF and the control subjects.. This study showed that K469E polymorphisms of ICAM1 that play a role in atherosclerotic pathogenesis are related to CSF.

Topics: Aged; Angiotensinogen; Coronary Artery Disease; Coronary Circulation; Coronary Vessels; Endothelium, Vascular; Female; Genotype; Humans; Intercellular Adhesion Molecule-1; Male; Middle Aged; Polymorphism, Genetic; Risk Factors

Angiotensinogen (AGT) constitutes a central component of the renin-angiotensin system that controls the systemic blood pressure and several other cardiovascular functions and may play an important role in atherosclerosis pathways. In this study, we employed TaqMan genotyping assays to evaluate the role of 8 AGT variants in primary hypertension (HTN), type 2 diabetes mellitus (T2DM), and obesity as a possible trigger of coronary artery disease (CAD) in a population of 4615 angiographed native Saudi individuals.. Linkage analysis was done by using the Affymetrix Gene Chip array, sequencing by using the MegaBACE DNA analysis system and genotyping accomplished by TaqMan chemistry using the Applied Biosystem real-time Prism 7900HT Sequence Detection System.. Six variants, rs2067853 GG [Odds ratio(95% Confidence Interval) = 1.44(1.17-1.78); p = 0.001], rs7079 [1.49(1.20-1.85); p < 0.0001], rs699 G [1.19(1.08-1.13); p < 0.0001], rs3789679 A [1.51(1.14-1.99); p = 0.004], rs2148582 GG [1.31(1.11-1.55); p = 0.002] and rs5051 TC + CC [1.32(1.13-1.60); p = 0.001] conferred risk for HTN (3521 cases versus 1094 controls). The rs2067853 (p = 0.042), rs699G (p = 0.007) and rs5051 (p = 0.051) also conferred risk for myocardial infarction (MI; 2982 vs 1633), while rs3789679 A (p < 0.0001) and GA + AA (p < 0.0001) as well as rs4762G (p = 0.019) were associated with obesity (1576 vs 2458). However, while these variants appeared to be also associated with CAD (2323 vs 2292), only the rs7079G (p = 0.035) retained its significant relationship. Interestingly, among the haplotypes constructed from these SNPs, the baseline 8-mer haplotype, GGTGGGGT (χ² = 7.02; p = 0.0081) and another GGCGGAGT (χ² = 5.10; p = 0.024), together with several of their derivatives were associated with HTN. T2DM was associated with two 8-mer haplotypes, GGTAGGAC (χ2 = 5.66; p = 0.017) and ATTGAGAC (χ² = 5.93; p = 0.015), obesity with GGCGGAGT (χ² = 9.49; p = 0.0021) and MI was linked to ATTGGGAC (χ² = 6.68; p = 0.010) and GGTGGGAT (χ² = 4.25; p = 0.039). Furthermore, several causative haplotypes were also shared among the risk traits as well as with CAD.. These results point to AGT as independently conferring risk for various cardiovascular traits, and possibly interacting with these traits in events leading to atherosclerosis.

Topics: Angiotensinogen; Arabs; Case-Control Studies; Chi-Square Distribution; Coronary Angiography; Coronary Artery Disease; Diabetes Mellitus, Type 2; DNA Mutational Analysis; Female; Gene Frequency; Genetic Linkage; Genetic Predisposition to Disease; Haplotypes; Humans; Hypertension; Logistic Models; Male; Middle Aged; Obesity; Odds Ratio; Oligonucleotide Array Sequence Analysis; Phenotype; Polymorphism, Single Nucleotide; Real-Time Polymerase Chain Reaction; Risk Assessment; Risk Factors; Saudi Arabia

This study examined renin-angiotensin-aldosterone (RAAS) system gene variants for associations with cardiovascular risk factors and outcomes in coronary heart disease. Coronary disease patients (n=1186) were genotyped for 21 single-nucleotide polymorphisms (SNPs) within angiotensinogen (AGT), angiotensin-converting enzyme (ACE), angiotensin-II type-1 receptor (AGTR1) and aldosterone synthase (CYP11B2). Associations with all-cause mortality and cardiovascular readmissions were assessed over a median of 3.0 years. The AGT M235T 'T' allele was associated with a younger age of clinical coronary disease onset (P=0.006), and the AGT rs2478545 minor allele was associated with lower circulating natriuretic peptides (P=0.0001-P=0.001) and E/E(1) (P=0.018). Minor alleles of AGT SNPs rs1926723 and rs11122576 were associated with more frequent history of renal disease (P0.04) and type-2 diabetes (P0.02), higher body mass index (P0.02) and greater mortality (P0.007). AGT rs11568054 minor allele carriers had more frequent history of renal disease (P=0.04) and higher plasma creatinine (P=0.033). AGT rs6687360 minor allele carriers exhibited worse survival (P=0.02). ACE rs4267385 was associated with older clinical coronary disease onset (P=0.008) and hypertension (P=0.013) onset, increased plasma creatinine (P=0.01), yet greater mortality (P=0.044). Less history of hypertension was observed with the AGTR1 rs12685977 minor allele (P=0.039). Genetic variation within the RAAS was associated with cardiovascular risk factors and accordingly poorer survival.

Topics: Age of Onset; Aged; Angiotensinogen; Comorbidity; Coronary Artery Disease; Cytochrome P-450 CYP11B2; Female; Gene Frequency; Genetic Predisposition to Disease; Humans; Hypertension; Kaplan-Meier Estimate; Linear Models; Male; Middle Aged; New Zealand; Odds Ratio; Peptidyl-Dipeptidase A; Phenotype; Polymorphism, Single Nucleotide; Prognosis; Proportional Hazards Models; Receptor, Angiotensin, Type 1; Renin-Angiotensin System; Risk Assessment; Risk Factors; Time Factors

Little is known about the contribution of genetics and lipoprotein subclasses to the development of coronary artery calcification (CAC) in asymptomatic, first-degree relatives of patients with CAD. We evaluated 100 asymptomatic, non-smoking, lipid-lowering therapy-naïve, first-degree relatives of patients with obstructive CAD through testing for 27 biomarkers, 15 single nucleotide polymorphisms in 12 candidate genes, and CAC and compared them to matched controls without family history. We compared prevalence of CAC in those with and without family history and biomarkers between those with and without CAC. Mean age was 41.6 ± 9 years; 58% were female. Significantly more subjects with family history had non-zero CAC (median Agatston: 13, range 1-1107) compared to those without family history (median Agatston: 43; range 1-345) (21% vs. 9%; p = 0.028). Among subjects with family history, in subjects with positive vs. negative CAC, multivariable analysis showed significantly lower HDL-2A (999 ± 333 vs. 1262 ± 397 nmol/L) and higher frequency of a substitution of threonine for methionine at codon 235 in the angiotensinogen gene (AGT M235T) (75% vs. 54%; p < 0.05; odds ratio of 2.6 for CAC). Population attributable risk of one copy of the risk allele at the AGT locus was 16%, highest of any variable tested. In conclusion, in this population of healthy, low-risk subjects with a family history of CAD, the AGT M235T variant was the most significant predictor of CAC independent of blood pressure, raising the possibility of an alternative biological pathway.

Topics: Adult; Aged; Amino Acid Substitution; Angiotensinogen; Biomarkers; Calcinosis; Calcium; Case-Control Studies; Coronary Artery Disease; Female; Humans; Male; Middle Aged; Polymorphism, Single Nucleotide; Prospective Studies; Risk Factors

Topics: Angiotensinogen; Calcinosis; Calcium; Coronary Artery Disease; Female; Humans; Male

Genetics polymorphism of the renin-angiotensin system (RAS) affects the pathogenesis of atherosclerosis and associated with coronary artery disease (CAD). We aimed to investigate the association between the RAS genes and premature CAD (PCAD) in Egyptians. 116 patients with PCAD, 114 patients with late onset CAD and 119 controls were included in the study. Angiotensin converting enzyme (ACE), angiotensin II receptor type 1 (ATR1) and angiotensinogen (AGT) genes polymorphisms were analyzed by polymerase chain reaction (PCR). We found that ACE DD, AGT TT and ATR1 CC increased the risk of PCAD by 2.7, 2.8 and 2.86 respectively). Smoking, hypertension, diabetes, total cholesterol, triglycerides and LDL cholesterol were independent risk factors for the development of PCAD. We conclude that the ACE DD, AGT TT and ATR1 CC genotypes may increase the susceptibility of an individual to have PCAD. The coexistence of CAD risk factors with these risky RAS genotypes may lead to the development of PCAD in Egyptian patients.

Topics: Adult; Aged; Angiotensinogen; Cholesterol; Coronary Artery Disease; Egypt; Female; Genetic Predisposition to Disease; Humans; Hypertension; Lipoproteins, LDL; Male; Middle Aged; Peptidyl-Dipeptidase A; Polymorphism, Genetic; Receptor, Angiotensin, Type 1; Renin-Angiotensin System; Risk Factors; Smoking; Triglycerides

The objective of this study was to explore the association between coronary artery disease and genetic polymorphisms of the renin-angiotensin-aldosterone system (RAAS) pathway. In addition, we examined the interactions between demographic and lifestyle risk factors (environmental factors including age, sex, smoking status, alcohol intake) and RAAS polymorphisms on disease risk.. A total of 1089 subjects who underwent coronary angiography were enrolled in this study. Eight RAAS polymorphisms were genotyped in this population: the G2350A (rs4343) polymorphism in exon 17 of the angiotensin converting enzyme (ACE) gene, 1166A→C (rs5186) and 573C/T (rs5182) in the angiotensin II type 1 receptor (AGTR1) gene, the -344C→T transversion (rs1799998) in the aldosterone synthase (CYP11B2) gene, and the G-217A (rs5049), G-6A (rs5051), M235T (rs699; T4072C), and T174M (rs4762; C3889T) polymorphisms in the angiotensinogen (AGT) gene. Subjects with coronary heart disease were defined as those with at least 50% stenosis in at least one major coronary artery, and, the severity of coronary atherosclerosis was defined by the Gensini scoring system.. Compared to the subjects with AA genotype, the subjects with AG + GG genotype of rs1799998 had significant lower gensini score (p=0.029). After adjusting for age, gender, cigarette smoking, and alcohol intake status, the AG genotype (OR 0.717 95%CI 0.541-0.950, p=0.021) and the AG + GG genotype (OR 0.730 95%CI 0.559-0.954, p=0.021) distributions of rs1799998 were significantly different between the cases and controls compare to the AA genotype. Subjects with three at-risk loci had increased risk of coronary artery disease compared to subjects carrying 0 or 1 risk-associated polymorphism (OR [95% CI]:1.579 [1.077-2.316], p=0. 019), and the significance of the association was not reduced after adjusting for age, sex, cigarette smoking, or alcohol intake (adjusted OR [95% CI]: 1.673 [1.116-2.507], p=0.013). The results of multifactor-dimensionality reduction analysis revealed an interaction effect of CYP11B2 -344C→T, age, and smoking status on the risk of coronary heart disease (training OR [95% CI]: 3.7685 [2.8463-4.9895], p<0.0001; testing OR [95% CI]: 2.7583 [1.2038-6.3203], p=0.015).. Subjects who carried the G allele of the rs1799998 polymorphism significantly associated with coronary heart disease and severity of coronary atherosclerosis estimated by the Gensini score in the whole population of the study. And, multiple RAAS gene polymorphisms are associated with coronary artery disease. The interaction of the CYP11B2 -344C→T polymorphism (rs1799998), age, and smoking status is also associated with enhanced risk of coronary artery disease.

Topics: Age Factors; Aged; Alcoholism; Alleles; Angiotensinogen; Case-Control Studies; Coronary Angiography; Coronary Artery Disease; Cytochrome P-450 CYP11B2; Epistasis, Genetic; Exons; Female; Gene-Environment Interaction; Genetic Loci; Genotype; Humans; Life Style; Male; Middle Aged; Odds Ratio; Peptidyl-Dipeptidase A; Polymorphism, Genetic; Receptor, Angiotensin, Type 1; Renin-Angiotensin System; Risk Factors; Smoking

Genetic factors contribute to the pathogenesis of coronary artery disease (CAD). We studied 100 patients with CAD and 50 healthy individuals to assess the association of endothelial nitric oxide (eNOS) polymorphism (Glu298Asp) and angiotensinogen polymorphisms (M235T) and CAD in an Egyptian population. Serum nitric oxide (NO) and angiotensin I levels were also measured. The frequency of Glu298Asp and M235T polymorphisms were higher in the CAD group compared with controls. The mean level of NO was significantly lower (P < .05) while angiotensin I was significantly higher (P < .05) in patients CAD than in controls. The frequency of eNOS TT allele of M235T variant was significantly higher in patients with CAD (20% vs 6%). The frequency of angiotensinogen (AGT) TT and T allele in patients with CAD was significantly higher (P < .05) than in controls (22% vs 6%and 47% vs23%, respectively). Homozygosity for Glu298Asp and M235T polymorphisms may predispose to CAD.

Topics: Adult; Angiotensin I; Angiotensinogen; Case-Control Studies; Cohort Studies; Coronary Artery Disease; Egypt; Female; Genetic Predisposition to Disease; Humans; Male; Middle Aged; Mutation; Nitric Oxide; Nitric Oxide Synthase Type III; Polymorphism, Genetic

Polygenetic effect has rarely been addressed in the genetic studies of coronary artery disease (CAD). We used the largest and ethnically homogeneous angiographic cohort to analyze multilocus data in renin-angiotensin system genes, and provide an explicit demonstration of gene-gene interactions.. A total of 1254 consecutive patients who underwent cardiac catheterization (735 with coronary artery disease and 519 without) were recruited. Angiotensin converting enzyme(ACE) gene I/D polymorphism; T174M, M235T, G-6A, A-20C, G-152A, and G-217A polymorphisms of the angiotensinogen (AGT) gene; and A1166C polymorphism of the angiotensin II type I receptor (AT1R) gene were genotyped. We used a regression approach based on a generalized linear model to evaluate haplotype effects, adjust non-genetic confounding effects and detect gene-gene interaction between ACE and AT1R genes.. We found significant differences in global AGT gene haplotype profile and individual haplotypes between cases and controls. Significant two-way and three-way gene-gene interactions between ACE I/D, AT1R A1166C polymorphisms and AGT gene haplotypes were detected. However, subjects carrying both D allele and GGCATC haplotype had an increased risk of CAD (odds ratio=1.63 [1.16-2.29]; P=0.004). We also used haplotype counting to directly estimate the odds ratio of each specific AGT gene haplotype, and found that the effects of haplotypes were markedly different in subgroups with different ACE or AT1R gene genotype.. The regression-based haplotype analyses permits simultaneous dectection of multi-locus and multi-gene effects in determining the risk of CAD. We provide the paradigm for genetic studies of complex-trait diseases using candidate genes based on biological pathways.

Topics: Aged; Angiotensinogen; Coronary Angiography; Coronary Artery Disease; Female; Genetic Predisposition to Disease; Haplotypes; Humans; Male; Middle Aged; Models, Genetic; Receptor, Angiotensin, Type 1; Renin-Angiotensin System; Risk Factors

Recent advances in molecular biology have made it possible to identify numerous polymorphisms of the renin-angiotensin system, which play an important role in the etiology of cardiovascular disease.. The aims of the study were (i) to assess the distribution of the angiotensin II type 1 receptor (AGTR1) gene 1166A/C polymorphism and two polymorphisms of the angiotensinogen (AGT) gene (Met235Thr and Thr174Met) in patients with ST-segment-elevation myocardial infarction (STEMI) who underwent coronary angiography, compared with healthy volunteers; (ii) to determine if there was any correlation between these polymorphisms and risk of STEMI; and (iii) to assess the association of the examined polymorphisms with such classic cardiovascular risk factors as hypertension, diabetes mellitus, obesity (based on a body mass index ≥25 kg/m2), smoking, dyslipidemia, and family history of cardiovascular disease.. A total of 100 patients (mean age 57 ± 10 years [range 31-76 years]; 21% women) with diagnosed STEMI and a control group consisting of 95 healthy volunteers (mean age 38 ± 11 years [range 17-60 years]; 20% women) were investigated for the AGTR1 1166A/C polymorphism and two variants of AGT (Met235Thr and Thr174Met). All patients received standard therapy for STEMI.. There were significant differences in the distribution of genotypes and the AGT Met174 allele for AGT Thr174Met polymorphism between patients and healthy subjects (p < 0.05). The AGTR1 1166A/C polymorphism genotype frequencies were significantly different in patients with hypertension compared with normotensive individuals. Specifically, the AGTR1 1166 AA genotype was twice as common in patients with hypertension as in those without (67% vs 33%), while the AC and CC genotypes were found predominantly in normotensive patients (p = 0.0016). The variant 1166C allele was much more common in patients without hypertension (67%) than in patients with hypertension (33%; p = 0.0006). The variant AGT Thr235 allele was more common in patients without a family history of cardiovascular disease than in patients with this risk factor (p < 0.05). The odds ratio (OR) for STEMI in patients with the heterozygous AGT 174 Thr/Met genotype was increased to 1.884 (95% confidence interval [CI] 1.03, 3.446; p < 0.05), while the OR calculated for carriers of the AGT Met174 allele was 2.038 (95% CI 1.129, 3.68; p = 0.0182). Significant genotypic associations of combinations of renin-angiotensin system gene polymorphisms in STEMI were not observed.. The most powerful predictive value for STEMI was represented by the Thr/Met genotype and the Met174 allele of the AGT Thr174Met gene polymorphism. In our study, in contrast to observations reported by other authors, the AA genotype of the AGTR1 1166A/C gene polymorphism - much more than other genotypes - was associated with hypertension.

Topics: Adult; Aged; Angiotensinogen; Coronary Artery Disease; Female; Genetic Predisposition to Disease; Genotype; Humans; Male; Middle Aged; Myocardial Infarction; Polymorphism, Genetic; Receptor, Angiotensin, Type 1; Renin-Angiotensin System; Risk Factors

We assessed the association between (CA)n repeat polymorphism of angiotensinogen (AGT), 250 base pair (bp) insertion/deletion (I/D) of angiotensin-converting enzyme (ACE), tetranucleotide repeat polymorphism (TCTG)n of renin (REN), (CT)n repeat polymorphism of the natriuretic peptide receptor A (NPRA) genes, and the presence and extent of coronary artery disease (CAD) in Greek patients with a history of myocardial infarction (MI). A total of 158 post-MI patients referred for coronary angiography were compared with 144 controls. The SS genotype of the AGT gene was related with an increased risk for 3-vessel CAD (odds ratio [OR], 1.94; 95% confidence interval [CI], 1.05-3.61; P = .041), whereas the SL genotype was related with a decreased risk (OR, 0.44; 95% CI, 0.22-0.87; P = .019). Moreover, there was a trend for the SL genotype of the REN gene toward increased risk for CAD. There was a significant association between (CA)n polymorphism of the AGT gene and the extent of CAD in Greek patients with a history of MI.

Topics: Aged; Angiotensinogen; Coronary Artery Disease; Female; Greece; Humans; Male; Myocardial Infarction; Peptidyl-Dipeptidase A; Polymorphism, Genetic; Receptors, Atrial Natriuretic Factor; Renin

Meta-analyses of genetic association studies are usually performed using a single polymorphism at a time, even though in many cases the individual studies report results from partially overlapping sets of polymorphisms. We present here a multipoint (or multilocus) method for multivariate meta-analysis of published population-based case-control association studies. The method is derived by extending the general method for multivariate meta-analysis and allows for multivariate modelling of log(odds ratios (OR)) derived from several polymorphisms that are in linkage disequilibrium (LD). The method is presented in a genetic model-free approach, although it can also be used by assuming a genetic model of inheritance beforehand. Furthermore, the method is presented in a unified framework and is easily applied to both discrete outcomes (using the OR), as well as to meta-analyses of a continuous outcome (using the mean difference). The main innovation of the method is the analytical calculation of the within-studies covariances between estimates derived from linked polymorphisms. The only requirement is that of an external estimate for the degree of pairwise LD between the polymorphisms under study, which can be obtained from the same published studies, from the literature or from HapMap. Thus, the method is quite simple and fast, it can be extended to an arbitrary set of polymorphisms and can be fitted in nearly all statistical packages (Stata, R/Splus and SAS). Applications in two already published meta-analyses provide encouraging results concerning the robustness and the usefulness of the method and we expect that it would be widely used in the future.

Topics: Angiotensinogen; Coronary Artery Disease; CX3C Chemokine Receptor 1; Genome-Wide Association Study; Humans; Hypertension; Linkage Disequilibrium; Meta-Analysis as Topic; Models, Genetic; Molecular Epidemiology; Multivariate Analysis; Odds Ratio; Polymorphism, Genetic; Polymorphism, Single Nucleotide; Receptors, Chemokine

There is increasing evidence suggesting the importance of evaluating gene-environment interactions in the genetic study of coronary artery disease (CAD). We investigated the association of multiple single nucleotide polymorphisms in the angiotensinogen (AGT) gene with CAD, considering the interaction between the genetic and non-genetic factors, using a larger and ethnically homogeneous angiographic cohort. A total of 1254 consecutive patients who underwent cardiac catheterization (735 with CAD and 519 without) were recruited. T174M (rs4762), M235T (rs699), G-6A, A-20C, G-152A, and G-217A polymorphisms of the AGT gene were genotyped. We used a regression approach based on a generalized linear model to evaluate haplotype effects defined by the multilocus data and detection of gene-environment interaction by incorporating interaction terms in the model. We found significant differences in global AGT gene haplotype profile between patients with and without CAD (the global score statistic=25.411, P=0.008). Significant interactions between AGT gene haplotypes, gender and hypertension were detected. We also used haplotype counting to directly estimate the odds ratio of each AGT gene haplotype, and found that the effects of haplotypes were markedly different in subgroups defined by gender and hypertension, providing strong evidence of gene-environment interaction. Female gender synergistically enhances (or male gender reverses) the effects of AGT gene haplotypes on the risk of CAD in the presence of hypertension. In conclusion, the effect of AGT gene haplotypes on the risk of CAD was significantly increased in women with hypertension, which highlights the importance of evaluating gene-environment interactions in the genetic study of CAD.

Topics: Angiography; Angiotensinogen; Cardiac Catheterization; Cohort Studies; Coronary Artery Disease; Female; Haplotypes; Humans; Hypertension; Male; Models, Genetic; Polymorphism, Genetic; Regression Analysis; Risk; Sex Factors

Several polymorphisms within the renin-angiotensin system cluster of genes have been associated with the advent of coronary artery disease (CAD) or related pathologies. We investigated the distribution of 5 of these polymorphisms in order to find any association with CAD development and distinguish if any of the biochemical and behavioural factors interact with genetic polymorphisms in the advent of the disease.. ACE I/D (rs4340), ACE A11860G (rs4343), AT1R A1166C (rs5186), AGT T174M (rs4762) and AGT M235T (rs699) gene polymorphisms were PCR-RFLP analysed in 298 CAD patients and 510 controls from Portugal. Several biochemical and behavioural markers were obtained.. ACE I/D DD and ACE11860 GG genotypes are risk factors for CAD in this population. The simultaneous presence of ACE I/D I and ACE11860 A alleles corresponds to a significant trend towards a decrease in CAD incidence. We found several synergistic effects between the studied polymorphisms and classical risk factors such as hypertension, obesity, diabetes and dyslipidaemia: the presence of the DD genotype of ACE I/D (and also ACE11860 GG) increases the odds of developing CAD when associated to each one of these classical risk factors, particularly when considering the male and early onset CAD subgroup analysis; AGT235 TT also increases the CAD risk in the presence of hypertension and dyslipidaemia, and AT1R1166 interacts positively with hypertension, smoking and obesity.. ACE polymorphisms were shown to play a major role in individual susceptibility to develop CAD. There is also a clear interaction between RAS predisposing genes and some biochemical/environmental risk factors in CAD onset, demonstrating a significant enhancement of classical markers particularly by ACE I/D and ACE11860.

Topics: Adult; Aged; Angiotensinogen; Coronary Artery Disease; Female; Gene Frequency; Genes, ras; Genetic Predisposition to Disease; Humans; Male; Middle Aged; Peptidyl-Dipeptidase A; Polymorphism, Genetic; Portugal; Risk Factors

Familial hypercholesterolemia is characterized by high plasma low-density lipoprotein cholesterol levels and premature coronary heart disease. Despite the monogenetic origin of familial hypercholesterolemia, the incidence of coronary heart disease varies considerably among patients, which is only partly explained by classical risk factors. Hypertension is an important risk factor for coronary heart disease that is associated with angiotensinogen levels. Therefore, we analyzed the angiotensinogen gene as a modifier gene for coronary heart disease risk in patients with familial hypercholesterolemia.. In a cohort of 1785 familial hypercholesterolemia patients, we reconstructed five frequent haplotypes of the angiotensinogen gene, based on four polymorphisms. The five haplotypes cover approximately 98% of the genetic diversity accounted for by these four polymorphisms. The associations between the haplotypes and coronary heart disease were analyzed with the haplo.stats program, adjusted for age, sex and smoking.. Patients homozygous for the C allele of the 4072 T>C polymorphism had a 34% increased coronary heart disease risk (P = 0.017) compared to patients homozygous for the T allele. Haplotype H3, consisting of the minor allele of the 4072T>C polymorphism and the major alleles of the other polymorphisms, had a frequency of 15% and was associated with a 45% increased coronary heart disease risk (P = 0.006) compared to the wild-type haplotype H1.. We conclude that genetic variation in the angiotensinogen gene contributes to coronary heart disease risk in patients with familial hypercholesterolemia.

Topics: Adult; Alleles; Angiotensinogen; Coronary Artery Disease; Female; Haplotypes; Humans; Hyperlipoproteinemia Type II; Male; Middle Aged; Polymorphism, Genetic

Atherosclerosis is an inflammatory disease resulting from interactions between various genetic and non-genetic factors. Angiotensinogen gene (AGT) belongs to polymorphic candidate genes. Recent evidence show that many traditional risk factors of coronary artery disease (CAD) influence synthesis of AGT. This report focuses on the interactions between M235T polymorphism of AGT gene and traditional risk factors of CAD.. 255 subjects, including 158 patients with angiographically confirmed CAD and 97 blood donors without history of cardiovascular diseases were studied. M235T polymorphism of the AGT gene was genotyped using PCR-RFLP method. To determine the possible interactions of AGT genotypes and traditional risk factors of CAD the attributable proportion due to interaction (AP) and synergy models were used.. The frequency of 235T allele carriers was significantly higher in patients than in controls (77.8 vs. 62.9, OR = 2.20, 95% CI; 1.10-4.40, P = 0.026, in multivariate logistic regression model). We found the existence of interaction between the 235T allele carrier-state and hypercholesterolemia (total cholesterol > or = 5 mmol/l) increasing the risk of CAD (SI = 3.39, 95% CI; 1.33-8.66, AP = 0.65, 95% CI; 0.39-0.91). The 235T allele also interacted with elevated LDL cholesterol levels (> or = 3 mmol/l) (AP = 0.49, 95% CI; 0.20-0.96), but not with the hypertension, overweight/ obesity and cigarette smoking.. The 235T allele increases the risk of CAD associated with the presence of hypercholesterolemia.

Topics: Adult; Angiotensinogen; Comorbidity; Coronary Artery Disease; Female; Genotype; Humans; Hypercholesterolemia; Logistic Models; Male; Middle Aged; Multivariate Analysis; Poland; Polymorphism, Genetic; Radiography; Risk Factors

There have been many reports regarding the association between renin-angiotensin system (RAS) gene polymorphisms and coronary artery disease (CAD) or acute myocardial infarction (AMI), but the results are inconsistent. In the present study, we used several new approaches with multilocus data to reappraise this issue in a large and relatively homogeneous Taiwanese population. A total of 1254 consecutive patients who underwent cardiac catheterization (735 with documented coronary artery disease and 519 without) between 1996 and 2003 were recruited. Angiotensin-converting enzyme gene insertion/deletion (I/D) polymorphism; T174M, M235T, G-6A, A-20C, G-152A and G-217A polymorphisms of the angiotensinogen gene; and A1166C polymorphism of the angiotensin II type I receptor gene were genotyped. In single-locus analyses, no locus was associated with CAD, history of AMI and three-vessel CAD, either with or without adjustment for conventional CAD risk factors. For multilocus analyses, we recreated a balanced population, with the controls individually matched to the cases regarding the conventional CAD risk factors. We found that the angiotensinogen gene haplotype profile was significantly different between the cases and controls (chi2=31.6, P=0.030) in haplotype analyses. Furthermore, significant three-locus (G-217A, M235T and I/D) gene-gene interactions were detected by multifactor-dimensionality reduction method (highest cross-validation consistency 10.0, lowest prediction error 40.56%, P=0.017) and many even higher order gene-gene interactions by multilocus genotype disequilibrium tests (16 genotype disequilibria exclusively found in the controls, all of which included at least two genes among AGT, ACE and AT1R genes). Our study is the first to demonstrate epistatic, high-order, gene-gene interactions between RAS gene polymorphisms and CAD. These results are compatible with the concept of multilocus and multi-gene effects in complex diseases that would be missed with conventional approaches.

Topics: Aged; Angiography; Angiotensinogen; Coronary Artery Disease; Epistasis, Genetic; Female; Humans; Linkage Disequilibrium; Male; Middle Aged; Myocardial Infarction; Peptidyl-Dipeptidase A; Polymorphism, Genetic; Renin-Angiotensin System; Taiwan

Coronary artery calcification (CAC) is an important indicator of future coronary artery disease events. Since elevated blood pressure (BP) is an important predictor of CAC, genetic polymorphisms in the renin-angiotensin system and their interaction may play a role in explaining CAC quantity variation.. As part of the Epidemiology of Coronary Artery Calcification Study, 166 asymptomatic women and 166 asymptomatic men were genotyped for the insertion/deletion polymorphism in the angiotensin-converting enzyme (ACE) gene and the -6 promoter polymorphism of the angiotensinogen (AGT) gene. We used a novel method to detect gene-gene interaction and compared it to the standard two-way analysis of variance (ANOVA) method.. Based on a two-way ANOVA model, there was no evidence for epistasis for either systolic BP or CAC in either men or women. However, using a novel method, we found evidence of significant gene-gene interaction in systolic BP in men and gene-gene interaction in both systolic BP levels and CAC quantity in women.. Our study demonstrates that new methods of assessing epistasis maybe important in understanding the complex genetics of systolic blood pressure as well as subclinical coronary atherosclerosis.

Topics: Adult; Aged; Aged, 80 and over; Angiotensinogen; Base Sequence; Blood Pressure; Calcinosis; Coronary Artery Disease; Coronary Vessels; DNA; Epistasis, Genetic; Female; Genotype; Humans; Male; Middle Aged; Peptidyl-Dipeptidase A; Polymorphism, Genetic; Promoter Regions, Genetic; Renin-Angiotensin System

Angiotensinogen and its cleaved forms angiotensin I and angiotensin II are important regulators of blood pressure. The gene for angiotensinogen (AGT) carries two common polymorphisms, T207M and M268T (previously described as T174M and M235T). To investigate the role of haplotypes formed by these polymorphisms for angiotensinogen levels we examined blood pressure, coronary artery disease (CAD), myocardial infarction (MI), and AGT genotypes and haplotypes in 2,575 patients with angiographically documented CAD and 731 individuals in whom CAD had been ruled out by angiography. Three haplotypes, designated as Hap1 (T207, M268), Hap2 (T207, T268) and Hap3 (M207, T268), accounted for more than 99% of alleles. The AGT Hap2 haplotype was significantly associated with angiotensinogen levels; one additional Hap2 allele accounted for an approx. 8% increase in angiotensinogen. This association was stronger than that of either single polymorphism. AGT genotypes or haplotypes were not related to hypertension, CAD or MI. We conclude that a common haplotype of the angiotensinogen gene is linked to angiotensinogen levels but has no major impact on blood pressure, hypertension, or cardiovascular risk.

Topics: Angiotensinogen; Blood Pressure; Coronary Artery Disease; Female; Haplotypes; Health; Homozygote; Humans; Male; Middle Aged; Polymorphism, Single Nucleotide; Risk Factors

Coronary artery bypass graft surgery is associated with a considerable 2-year mortality rate. Gene polymorphisms of the renin-angiotensin system may be associated with the risk of hypertension and cardiovascular disease. The angiotensin I-converting enzyme DD genotype has recently been identified as independent predictor of the outcome after coronary artery bypass graft surgery. Genetic factors of the clotting system may be related to the risk of myocardial infarction and restenosis after coronary interventions. The aims of the present study were to investigate whether gene polymorphisms of the renin-angiotensin system (angiotensinogen 235 M/T, angiotensin II type 1 receptor 1166 A/C) or the clotting system (glycoprotein IIIa PlA1/PlA2 and factor V Leiden 1691 G/A) are associated with the outcome after coronary artery bypass grafting.. A study population of 247 patients was followed-up 2 years after coronary artery bypass graft surgery. The primary end-point was total mortality. The secondary end-point was mortality from cardiac cause or the need for myocardial revascularization (percutaneous coronary interventions or recurrent surgery) during follow-up. Geno typing was performed by polymerase chain reaction- and restriction fragment length polymorphism-based techniques.. An older age and the non-use of the internal mammary artery graft were identified as independent predictors of the primary end-point after coronary artery bypass grafting. A decreased left ventricular ejection fraction was an independent predictor for the secondary end-point. No association was found between any of the genetic factors and the outcomes after coronary artery bypass graft surgery in the main factor regression models. However, the angiotensin II type 1 receptor 1166 A/C gene polymorphism modulated the effects of age on the primary end-point, and the angiotensinogen 235 M/T gene polymorphism modulated the effects of age on the secondary end-point.. We conclude that there are interactions between the angiotensin II type 1 receptor 1166 A/C as well as the angiotensinogen 235 M/T gene polymorphism and age with respect to the outcome after coronary artery bypass graft surgery. The glycoprotein IIIa PlA1/PlA2 and the factor V Leiden 1691 G/A gene polymorphisms were not associated with mid-term mortality or cardiac morbidity after coronary artery bypass grafting.

Topics: Adult; Aged; Aged, 80 and over; Alanine; Angiotensinogen; Blood Coagulation; Blood Pressure; Coronary Artery Bypass; Coronary Artery Disease; Cysteine; Factor V; Female; Follow-Up Studies; Genotype; Humans; Integrin beta3; Male; Methionine; Middle Aged; Myocardial Contraction; Polymorphism, Genetic; Receptor, Angiotensin, Type 1; Renin-Angiotensin System; Stroke Volume; Threonine; Treatment Outcome

Previous reports relating coronary artery disease and functional variants of the renin-angiotensin system have been contradictory in establishing the role of these polymorphisms in coronary artery disease (CAD) development. The aim of the present study is to determine if there is an association between the M235T variant of the angiotensinogen gene and severity of coronary artery disease in patients with clinically suspected disease undergoing cineangiogram.. The angiotensinogen M235T variant was analyzed in 871 consecutive patients with clinically suspected coronary artery disease submitted to coronary angiography study. Three different angiographic scores were used to determine severity of the disease analyzing 20 coronary segments. All patients were evaluated considering classical risk factors for coronary artery disease throughout a medical oriented questionnaire, anthropometric measures, and blood glucose and lipid profile determination.. Presence of the 235T allele was associated with higher angiographic extension scores in univariate analysis (p < 0.05). The 235T allele was also associated with an increased risk of presenting 3-vessel disease (p < 0.05). In addition, the T allele was significantly associated with higher Gensini's scores both in univariate (p = 0.05) and multivariate analyses (p < 0.05). Finally, a 1.86 fold increase in the risk of multivessel disease (95% CI: 1.174-2.947) was associated with the TT genotype independently of other cardiovascular risk factors associated with disease extension.. The data hereby provide further support for the association between angiotensinogen M235T polymorphism and CAD severity independently of other cardiovascular risk factors.

Topics: Angiotensinogen; Coronary Artery Disease; Female; Humans; Male; Methionine; Middle Aged; Polymorphism, Genetic; Risk Factors

Genes encoding components of the renin-angiotensin system have been associated with elevated blood pressure (BP) and an increased risk of coronary artery disease. To explore the role of the angiotensinogen (AGT) gene in coronary atherosclerosis and thrombosis, we studied the effect of the AGT M235T gene variant on plasma AGT levels and BP in patients with coronary artery disease and in the subgroup of survivors of myocardial infarction as compared with angiographically defined control subjects.. This was a case-control study of 301 white male subjects examined at Frankfurt University medical center. Plasma AGT levels increased stepwise according to the number of T235 alleles present (no T235 allele, 14.8 +/- 3.9 nmol/L; 1 allele, 15.7 +/- 5.1 nmol/L; 2 alleles, 17.3 +/- 4.7 nmol/L; P =.006). In a multivariate model, circulating AGT emerged as the most important predictor of diastolic pressure (P =.001). In addition, AGT M235T gene polymorphism remained a significant predictor of diastolic BP in a multivariate model adjusted for age, body mass index, fasting glucose, apolipoprotein B, presence of coronary artery disease, and treatment with antihypertensive agents ( P <.05). Finally, homozygosity for T235 was associated with increased univariate risk of coronary artery disease and myocardial infarction (odds ratio estimates 1.5; 95% confidence intervals 1.1 to 2.1, P =.03, and 1.0 to 2.1, P =.05, respectively).. The significant relations observed between the AGT M235T variant, its protein product, and the cardiovascular disease phenotypes provide evidence for a possible role of elevated circulating AGT in the pathogenesis of coronary artery disease.

Topics: Alleles; Angiotensinogen; Blood Pressure; Cardiovascular Diseases; Case-Control Studies; Coronary Artery Disease; Coronary Thrombosis; Gene Frequency; Genotype; Humans; Male; Middle Aged; Multivariate Analysis; Myocardial Infarction; Odds Ratio; Peptidyl-Dipeptidase A; Polymorphism, Genetic; Renin-Angiotensin System; Risk Factors

The relations of the angiotensinogen (AGT) T174M and M235T gene polymorphisms to the risk of coronary heart disease (CHD) have been investigated in only a few studies with conflicting results.. Therefore, we analysed the relationship of the AGT gene polymorphisms to the presence and extent of CHD in 2250 male Caucasians whose coronary anatomy was defined by means of coronary angiography. The relative frequencies of the T and M alleles of the T174M and of the M235T gene variation did not significantly differ between patients without or with single-, double- or triple-vessel disease and between subjects without or with myocardial infarction (MI). In contrast the mean CHD score--defined by Gensini--was higher within MM homozygotes of the T174M gene variation than within TT genotypes; TM subjects had intermediate values. In M235T genotypes, mean CHD scores were similar in the total sample and in older individuals (> or = 62 years), whereas in younger individuals (< 62 years) a higher CHD score was found within AGT 235 T allele carriers than within MM homozygotes. In younger individuals with high apoAI plasma levels, the mean CHD score was clearly higher within TT homozygotes of the M235T gene variation than within MM genotypes; MT subjects had intermediate values. An interaction between both angiotensinogen gene polymorphisms on the extent of CHD or on the risk of non-fatal MI were not observed when the M allele of AGT T174M was combined either with the T allele or the TT genotype of M235T.. The present study strengthens the hypothesis of an association of both angiotensinogen gene polymorphisms with the extent of coronary heart disease.

Topics: Alleles; Angiotensinogen; Apolipoprotein A-I; Apolipoproteins B; Codon; Coronary Angiography; Coronary Artery Disease; Gene Frequency; Genetic Markers; Genotype; Humans; Linkage Disequilibrium; Male; Middle Aged; Polymorphism, Genetic; Risk Factors; Severity of Illness Index

Topics: Angiotensinogen; Coronary Artery Disease; Gene Frequency; Genes; Genotype; Humans; Patient Selection; Polymorphism, Genetic; Sample Size

A positive association was previously reported between angiotensin-converting enzyme (ACE) gene polymorphism and several cardiovascular diseases, such as myocardial infarction, left ventricular hypertrophy, and restenosis after percutaneous transluminal coronary angioplasty. Plasma ACE activity and carotid-wall thickening measured by ultrasonography were related, and it was postulated that long-term exposure to high levels of plasma ACE could be involved in structural changes of the arterial wall. In addition, angiotensinogen gene mutation was recently reported to be associated with essential hypertension and preeclampsia. There exists a possibility that the renin-angiotensin system plays an important role in the progress of cardiovascular diseases in humans. Therefore, we examined the association between the molecular variant of the angiotensin gene and coronary atherosclerosis.. This study included 82 patients who had coronary atherosclerosis and 160 control subjects; all study participants were Japanese. All patients with coronary atherosclerosis had at least one coronary artery with > 25% luminal diameter obstruction on average according to multiple coronary angiographic views. Angiotensinogen gene molecular variants were designated AA, Aa, and aa. The a allele indicated thymine-cytosine transition at nucleotide 704 in exon 2. Genomic DNA was extracted from peripheral blood leukocytes. Polymerase chain reaction was performed to amplify the concerned region of the angiotensinogen gene. After restriction enzyme digestion, it was possible to distinguish the molecular variant of the angiotensinogen gene. The frequencies of these genotypes were 7.3%, 26.8%, and 65.9% in the patients and 18.8%, 31.9%, and 49.3% in the control subjects for the AA, Aa, and aa alleles, respectively. There was an excess in the a allele among patients (P < .01).. We found a significant association between coronary atherosclerosis and a molecular variant of the angiotensin gene. The results suggested that the molecular variant of the angiotensinogen gene could be a new risk factor for coronary atherosclerosis.

Topics: Angiotensinogen; Coronary Artery Disease; Electrophoresis, Polyacrylamide Gel; Female; Gene Frequency; Genes; Genetic Variation; Genotype; Humans; Male; Middle Aged; Point Mutation; Polymerase Chain Reaction; Risk Factors