Association of endothelial nitric oxide synthase promoter region (T-786C) gene polymorphism with acute coronary syndrome and coronary heart disease.

BACKGROUND: Nitric oxide (NO) is an endothelium derived relaxing factor (EDRF) which has an important role for regulating the heart-vessel physiology. The objective of this study was to evaluate the effects of the eNOS T-786C polymorphism on lipid parameters and the development of acute coronary syndrome (ACS) and coronary heart disease (CHD) for the first time in a Turkish study group. We have analyzed the genotype frequencies of the T-786C polymorphism of the eNOS gene in 10 ACS patients (5 men, 5 women), 20 CHD patients (14 men, 6 women), and 31 controls (10 men, 21 women), who were angiographically proven to have normal coronaries. RESULTS: The demographic, biochemical and left ventricule systolic dysfunction data of the ACS, CHD patients and controls were analyzed as a function of eNOS T-786C genotypes. The eNOS gene T-786C polymorphism frequencies for T/T, C/T and C/C genotypes were respectively 10%, 40%, 50% in subjects with ACS; 75%, 20%, 5% in subjects with CHD and 67.7%, 25.8%, 6.5% in the control group. Significant difference was observed in genotype frequencies between the study groups for T-786C polymorphism (p = 0.001). The CC genotype frequency was found to be the most prevalent in ACS group in comparison to CHD and control groups (p = 0.001). TT was the most frequently observed genotype in both CHD patients and controls (p = 0.001). Left ventricule systolic dysfunction frequency was found to be highest in C/T genotype carriers (66.7%) in patients (ACS+CHD). None of the patients with LVSD were carrying the normal genotype (T/T). The eNOS T-786C polymorphism was not found to be effective over any analyzed lipid variable in patients (ACS+CHD). The HDL-cholesterol levels were found to be lower in CHD group were compared to controls (p < 0.01), whereas glucose and leucocyte levels of the ACS and CHD groups were both higher than controls (p < 0.001). CONCLUSION: The significantly high frequency of eNOS -786C/C genotype in ACS patients than in those of controls, indicate the genotype association with ACS. The finding of significantly high frequency of T/T genotype in the CHD group, may support the relationship of CC genotype with ACS without CHD. The high frequency of the mutant (C/C) and heterozygous (C/T) genotypes found may be linked to left ventricule remodeling after MI.

Apolipoprotein E polymorphism in Turkish subjects with Type 2 diabetes mellitus: allele frequency and relation to serum lipid concentrations.

The role of apolipoprotein E (apoE) genotypes in modulating plasma lipid and apolipoprotein levels was studied in 112 patients with Type 2 diabetes mellitus (T2DM) and 94 healthy individuals. ApoE genotypes were identified by PCR amplification and subsequent restriction endonuclease digestion. The apoE allele and genotype frequencies were similar in both the diabetic and control subjects. The apoE allele frequencies were found to be 74.3 for e3, 10.1 for e2, 15.6 for e4 in the diabetic group, and 68.1 for e3, 13.2 for e2 and 18.7 for e4 in the control group. Sex-specific genotypic distribution of apoE polymorphism did not differ between the study groups. To elucidate the association of apoE with lipid abnormalities with respect to gender, serum lipid and apolipoprotein levels were compared among apo e2 (e2/2 and e3/2), e3 (e3/3) and e4 (e4/3 and e4/4) groups of T2DM and control subjects. Apo e2 allele was found to be associated to triglycerides for both sexes, and associated to glucose, and BMI only in females. Subjects with e2 allele had higher levels of BMI, glucose and triglyceride in comparison to e3 and e4. Our data suggest that genetic variation at the apoE locus in Turkish subjects is a genetic factor that influences lipid levels. Further studies attempting to correlate apoE polymorphism with lipid profile in a large number of individuals would be helpful in establishing the true significance of this polymorphism in the Turkish population.

The interrelationship between insulin secretion and action in type 2 diabetes mellitus with different degrees of obesity: evidence supporting central obesity.

This paper investigates the relative role of the impairment of insulin secretion and action in the pathogenesis of Type 2 diabetes mellitus (T2DM). The parameters indicating insulin secretion and action were calculated from the data obtained during oral glucose tolerance test (OGTT), in 156 age- and sex-matched T2DM patients divided in 4 groups according to their body mass index (BMI, I = 20.0-24.9, II = 25.0-29.9, III = 30.0-39.9 and IV > 40.0 kg/m2). After obtaining baseline biomedical parameters (plasma glucose, serum insulin, cholesterol, HDL-cholesterol, triglycerides, BMI, and amount of fat tissue), the rates of insulin secretory capacity and insulin action were obtained from OGTT and compared between the T2DM patients with normal body weight and different grades of obesity. Beta-cell secretory capacity of the participants was found to be proportionally and significantly higher in graded obese than that of the normal body weight patients. The rates of hepatic as well as peripheral insulin resistance in obese groups proportionally and significantly rise in comparison with that of non-obese diabetics. In addition, these parameters are shown to be related to the body fat, presumably visceral in origin. In conclusion, hyperglycemia-hyperinsulinemia observed in obese and T2DM patients might be due, in part, to increased capacity of insulin secretion, and to exaggerated hepatic glucose production because of hepatic insulin resistance, respectively.