Relationship between an Angiotensinogen Gene Polymorphism (M235T) and Serum Lipids: A Cross-Sectional Study among Japanese Workers

Angiotensinogen (AGT) is a component of the renin-angiotensin system, which plays a central role in blood pressure regulation. Although it is controversial, the association between AGT gene polymorphisms and hypertension, and coronary heart disease is suspected. In a case-control study on the metabolic syndrome, an association between AGT M235T polymorphism and serum total cholesterol (TC) level was demonstrated by Thomas et al. (2001). To reconfirm this relationship, a cross-sectional study among Japanese workers with 876 dyslipidemia and 1,158 non-dyslipidemia subjects was carried out. To evaluate the AGT M235T polymorphism, a PCR-mutant allele specific amplification (MASA) method was employed. No significant difference in the distribution of genetic variance was observed between the two groups. Although it was not significant, the T allele correlating to the lower TC of the present study occurred in a reversed manner to the previous report. In our results, no significant association between AGT M235T and TC was observed

Effects of Glu298Asp Polymorphism of Endothelial Nitric Oxide Synthase (eNOS) Gene on eNOS mRNA and Protein Expressions in Cultured Human Vascular Endothelial Cells

The relationship between cardiovascular disease and Glu298Asp polymorphism of nitric oxide synthase (eNOS) gene in vascular endothelial cells is controversial due to conflicting results. To demonstrate the effects of Glu298Asp polymorphism of the eNOS gene on eNOS gene expression by excluding the effects of various confounding factors, eNOS mRNA and protein expressions were measured using cultured human umbilical vein endothelial cells (HUVECs) according to genotypes of Glu298Asp polymorphism of the eNOS gene. eNOS mRNA expression was measured by real-time PCR/reverse trasnscription-PCR. eNOS protein expression was measured by an immunoassay method. HUVECs with Glu298Asp tended to show higher eNOS mRNA and protein expressions than those with Glu298Glu, but the difference was not significant. These results suggest that the genotypic difference of Glu298Glu and Glu298Asp has no effect on eNOS mRNA and protein expressions

A Molecular Variant of the Angiotensinogen Gene and Hypertension in a Case-Control Study in Japanese

In order to examine the distribution of M235T (the substitution of threonine for 0methionine at position 235 codon) polymorphism genotypes of the angiotensinogen (AGT) gene and the relationship between M235T polymorphism of the AGT gene and hypertension, a descriptive study and a case-control study were performed among Japanese workers. The subjects were 2042 workers at an occupational site in Shimane Prefecture in Japan. The database was set up for the workers' regular health examination in 1998. The M235T polymorphism of the AGT gene for each worker was defined by the mutant allele specific amplification (MASA) method. The rates of M235M (MM), M235T (MT) and T235T (TT) genotypes were 3.9%, 30.7% and 65.5%, respectively. The odds ratios of MT and TT against MM for hypertension by univariate analysis were 0.77 [95% confidence interval (CI) 0.27-2.18] and 0.77 (95% CI 0.28-2.14), respectively. The odds ratios of MT and TT against MM for hypertension, adjusted for body mass index, fasting blood sugar, drinking habits, cigarette smoking and exercise in a logistic regression model, were 0.90 (95% CI 0.29-2.74) and 0.87 (95% CI 0.30-2.58), respectively. The data from this study suggests that there may be no relationship between the M235T polymorphism of the AGT gene and hypertension. Further prospective studies are needed to resolve this issue