angiotensinogen and Cerebral-Infarction

To investigate the relationship of four single nucleotide polymorphism (SNP) haplotypes in the angiotensinogen (AGT) gene to the primary hypertension with or without cerebral infarction in the Li nationality of Hainan, China.. Total 300 subjects were allocated into three different groups: Group 1, 100 patients who have primary hypertension; Group 2, 100 patients who have primary hypertension with cerebral infarction; and control group, 100 healthy individuals. The genotypes of all subjects were determined by PCR-sequencing to analyze the four polymorphisms at position -152 (G-A), -20 (A-C), -18 (C-T), and -6 (A-G) in the promoter region of AGT.. The frequencies of CT genotype of AGT-18 and T allele in Group 1 (P = 0.003, P = 0.004) and Group 2 (P = 0.002, P = 0.002) were both significantly higher than in healthy controls. The frequency of G allele of AGT-6 was significantly higher in Group 2 than in the control group (P = 0.016), while there is no significant difference between Group 1 and the control. Haplotype analysis revealed that H6 haplotype frequency which included -20C and -6G was significantly increased in Group 2 (P = 0.003) compared with the control group, while H5 haplotype frequency which included -20C and -18T was significantly increased in Group 1 (P = 0.006) versus the control.. The -20 (A-C) and -18 (C-T) of the AGT may play an important role in pathogenesis of primary hypertension; and -20 (A-C), -18 (C-T), and -6 (A-G) may be the genetic risk factors for the onset of primary hypertension with cerebral infarction in the Li nationality of Hainan, China.

Topics: Angiotensinogen; Cerebral Infarction; China; Female; Genetic Predisposition to Disease; Genotype; Haplotypes; Humans; Hypertension; Male; Middle Aged; Polymerase Chain Reaction; Polymorphism, Single Nucleotide

Sasang constitutional medicine is a major branch of Korean traditional Oriental medicine. The differences of disease susceptibility to be shown in Sasang constitution may be due to genetic factors. Therefore, the authors examined relationship between candidate genes of cerebral infarction (CI) and Sasang constitution. The homozygous deletion allele of the angiotensin converting enzyme gene (ACE/DD), homozygous threonine allele of the angiotensinogen gene (AGN/TT), and the e4 allele of the apolipoprotein E gene (ApoE/e4) are reported to be associated with ischemic heart disease. CI is another atherosclerotic disease; and the effects of these polymorphisms on CI have been confusing. This study investigated whether ACE/DD, AGN/TT, and ApoE/e4 genotypes are associated with CI and whether genetic risk is enhanced by Sasang constitutional classification. The authors ascertained these genotypes in patients with CI (N=211), diagnosed by brain computed tomography. Control subjects for the infarction group were randomly selected from 319 subjects matched for age, sex, and history of hypertension with patients. The ACE/DD genotype was not associated with CI. However, there was significant association between ApoE polymorphism and CI (chi2=15.089, p<.05). Furthermore, frequency of AGN/TT genotype was higher in the patients with CI than in the controls (chi2=20.072, p<.05). The frequency of T allele was 0.91 in patients and 0.82 in controls (chi2=17.237, p<.05). However, Sasang constitutional classification did not increase the relative risk for CI in the subjects with ApoE/e4 or AGN/T allele. These results suggest that ApoE and AGN polymorphism predict CI, but Sasang constitutional classification does not enhance the risk for CI associated with ApoE/e4 or AGN/TT in a Korean population.

Topics: Angiotensinogen; Apolipoproteins E; Body Constitution; Brain; Cerebral Infarction; DNA Primers; Female; Gene Frequency; Genotype; Humans; Korea; Male; Middle Aged; Peptidyl-Dipeptidase A; Polymerase Chain Reaction; Polymorphism, Genetic

Lacunar infarction is a unique stroke entity with characteristic symptoms. However, it is often silent clinically. The possible genetic predisposition to symptoms of lacunar infarction was investigated.. One-hundred and fifty-one patients with lacunar stroke were consecutively recruited. Lacunar stroke was diagnosed based on both neurological symptoms and lacunar lesion(s), demonstrated by MRI, that were responsible for the symptoms. One-hundred and fifty control subjects with MRI-proven lacunar lesions without neurological symptoms served as controls. There was no significant difference in age, sex and prevalence of known risk factors between cases and controls. Insertion and deletion polymorphisms of the angiotensin-converting enzyme gene (ACE), M235T substitution of the angiotensinogen gene (AGT), and A1133C substitution of type 1 receptor of the angiotensin II gene were determined.. The frequency of ACE D allele was significantly higher in symptomatic patients compared with asymptomatic subjects (0.44 vs. 0.36, p < 0.05). The genotype distribution of AGT was significantly different between symptomatic and asymptomatic patients (chi(2) = 6.6, p = 0.037). Multiple logistic regression analysis revealed that ACE gene and AGT genotypes were independently associated with the neurological manifestation of lacunar infarction. In subjects with 1 lacuna, the odds ratio of the ACE DD genotype for symptomatic manifestation was 4.98 (95% CI 1.25-19.9). In subjects with 4 or more lacunae, the odds ratio of the ACE II genotype for symptomatic manifestation was 0.24 (95% CI 0.10-0.56). Furthermore, the ACE gene polymorphism was significantly different between symptomatic patients with a single lacuna and asymptomatic subjects with 4 or more multiple lacunar infarctions (chi(2) = 10.6, p = 0.005).. These findings suggest that 2 subtypes of lacunar infarction, single symptomatic lacuna and multiple asymptomatic lacunae, may possess different genetic backgrounds. Subjects with the ACE DD genotype could be more predisposed to be symptomatic in first-ever lacunar stroke, while the ACE II genotype may convey resistance to symptoms even after multiple lacunar strokes. Polymorphism of genes of the renin-angiotensin system could be involved in the manifestation of neurological symptoms of lacunar infarction.

Topics: Age Factors; Aged; Alleles; Angiotensinogen; Angiotensins; Case-Control Studies; Cerebral Infarction; Female; Gene Frequency; Genotype; Humans; Magnetic Resonance Imaging; Male; Odds Ratio; Peptidyl-Dipeptidase A; Polymorphism, Genetic; Receptors, Angiotensin; Renin-Angiotensin System; Risk Factors; Sex Factors; Stroke

The homozygous deletion allele of the angiotensin-converting enzyme gene (ACE/DD), homozygous threonine allele of the angiotensinogen gene (AGN/TT), and the epsilon4 allele of the apolipoprotein E gene (apoE/epsilon4) are reported to be associated with ischemic heart disease. Cerebral infarction (CI) is another atherosclerotic disease, and the effects of these polymorphisms on CI have been confusing. The frequency of the DD genotype of the ACE gene, but not the TT genotype of the AGN gene and the epsilon4 allele of ApoE, was significantly higher in subjects with than those without CI in Japan. In this study, we investigated whether ACE/DD, AGN/TT, and apoE/epsilon4 genotypes are associated with CI and whether genetic risk is enhanced by the effect of one upon another. We ascertained these genotypes in patients with CI (n = 365), diagnosed by brain computed tomography. Control subjects for the infarction group were randomly selected from 319 subjects matched for age, gender, and history of hypertension with patients. The ACE/DD genotype was not associated with CI. Frequency of the AGN/TT genotype was higher in patients with CI than in controls (chi2 = 12.287, p < 0.05). The frequency of t allele was 0.88 in patients and 0.82 in controls (chi2 = 11.041, p < 0.05; odds ratio, 1.7). Furthermore, the AGN/TT genotype increased the relative risk for CI in subjects with the ACE/DD genotype (chi2 = 7.8, p < 0.05; odds ratio, 1.9). There was no significant association between apoE/epsilon4 and CI. These results suggest that AGN/TT predicts CI and ACE/DD enhances the risk for CI associated with AGN/TT in a Korean population.

Topics: Aged; Angiotensinogen; Apolipoprotein E4; Apolipoproteins E; Brain; Cerebral Infarction; DNA Mutational Analysis; Female; Gene Frequency; Genetic Predisposition to Disease; Genetic Testing; Genotype; Humans; Korea; Male; Odds Ratio; Peptidyl-Dipeptidase A; Polymorphism, Genetic; Risk; Risk Factors; Tomography, X-Ray Computed

To detect the relationship between angiotensinogen (AGT) gene CD235 Met-->Thr substitution polymorphism and brain infarction.. The CD235Met-->Thr substitution polymorphism in exon 2 of AGT gene was analyzed in normal group(82 cases) and brain infarction group (102 cases) by a combination of polymerase chain reaction-restriction fragment length polymorphism(PCR-RFLP).. Between the control group and brain infarction group, chi-square test showed no significant difference in the frequencies of T/T genotype and T allele (P>0.05). However, the frequencies of T/T genotype and T allele (70.6% and 83.8%) for multiple brain infarction patients were higher than those (42.6% and 65.2%) for lacunae brain infarction patients and those (42.0% and 65.2%) for controls (P<0.01). The frequencies of AGT T/T genotype and T allele (65.3% and 78.6%) for patients with brain infarction associated with hypertension were higher than those (42.0% and 65.0%) for patients with brain infarction not associated with hypertension (P<0.05).. No direct relationship between AGT CD235 Met-->Thr substitution polymorphism and ordinary brain infarction has been observed, but there is a significant correlation between AGT gene T/T genotype and multiple brain infarction, and brain infarction associated with hypertension too.

Topics: Adult; Aged; Aged, 80 and over; Alleles; Angiotensinogen; Cerebral Infarction; Female; Genotype; Humans; Male; Middle Aged; Polymorphism, Genetic