angiotensinogen and Coronary-Thrombosis

To investigate the distribution frequencies of angiotensin-converting enzyme (ACE), angiotensinogen (AGT), angiotensin II I type receptor (AT1R) genotypes in Chinese, to find the relationships between polymorphisms of ACE, AGT and AT1R gene, and coronary artery thrombosis disease (CATD) and to study the interactions of themselves, PCR and PCR-RFLP techniques were performed to determine the genotypes of ACE, AGT and AT1R gene in CATD group (192 cases) and control group (110 cases). The results showed that (1) genotype frequencies of the three polymorphisms in the control group were 12.2% (DD), 43.9% (ID), and 43.9% (II) for the ACE I/D polymorphism; 8.2% (MM), 36.7% (MT), and 55.1% (TT) for AGT M235T polymorphism; 91.8% (AA), 8.2% (AC) for AT1R A1166C polymorphism respectively; (2) there were no significant differences between patients in either the control group, the non-MI group, or the MI group in any genotype frequency of all these three genes (P >0.05). (3) the odds ratio for CATD in subjects carrying both AT1R-AC and AGT-TT genotype was 3.517 (95% CI 0.988 - 12.527), compared with those carrying AT1R-AA and AGT-TT genotype and was 15.000 (95% CI 1.940-115.963), compared with those carrying AT1R-AC and AGT-MM/MT genotype. In subjects with AT1R-AC genotype, there was also a great difference of ACE D allele frequency between control group and CATD group (P=0.017). It is concluded that genotype frequencies of ACE I/D polymorphism, AGT M235T polymorphism, and AT1R A1166C polymorphism were obviously different from those in western countries. Although these three polymorphisms were not independent risk factors for CATD or myocardial infarction (MI) in Chinese, AT1R-AC genotype has a significant synergistic effect with AGT-TT genotype. There is also a obvious interaction between AT1R-AC genotype and ACE D allele.

Topics: Angiotensinogen; Coronary Thrombosis; Genotype; Humans; Peptidyl-Dipeptidase A; Polymorphism, Genetic; Receptor, Angiotensin, Type 1

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