Taq1B polymorphism of cholesteryl ester transfer protein (CETP) gene in primary combined hyperlipidaemia.

Background & objectives: Cholesteryl ester transfer protein (CETP) gene polymorphism is known to be associated with changes in lipid profiles. Primary hyperlipidaemia is considered to be a major risk factor for pancreatitis, atherosclerosis and coronary heart disease. We investigated the association of one common polymorphism in the CETP gene (Taq1B) with plasma lipid levels and CETP activity in Iranian subjects with and without primary combined hyperlipidaemia. Methods: The study included 102 patients with primary combined hyperlipidaemia and 214 health individuals. Polymerase chain reaction and restriction fragment length polymorphisms were used for genotype detection. To determine the relationship between Taq1B polymorphism and lipid levels, lipids and CETP activity were measured in primary combined hyperlipidaemic and normolipidaemic subjects, with and without Taq1B polymorphism. Results: Plasma CETP activity was significantly (P<0.001) higher in primary combined hyperlipidaemic individuals than in controls. Plasma HDL-C was higher in both groups, in the B2B2 genotype than in the B1B1 and B1B2 genotypes, whereas the serum TG concentrations and CETP activity were lower in B2B2 genotype compared with other genotypes (B1B1 and B1B2). The genotype and allelic frequencies for this polymorphism differed significantly between hyperlipidaemic and nonmolipidaemic individuals (P<0.05). In both groups, CETP Taq 1B polymorphism (presence of B2 allele) correlated significantly with HDL-cholesterol (HDL-C) (r=0.201 and r=0.452 in control and patient groups respectively) and CETP activity (r= -0.123 for controls and r= -0.192 for patients). Interpretation & conclusions: The results showed that Taq 1B polymorphism of CETP gene was associated with changes in lipids profile and plasma CETP activity in the selected population and might have a role in contributing to genetic risk of developing coronary artery disease.

Endothelial nitric oxide synthase gene intron4 VNTR polymorphism in patients with coronary artery disease in Iran.

BACKGROUND & OBJECTIVES: Endo-derived nitric oxide (NO) is synthesized from L-arginine by endothelium nitric oxide synthase (eNOS) encoded by the NOS3 gene on chromosome7. Since reduced NO synthesis has been implicated in the development of coronary atherosclerosis; polymorphisms of NOS gene might be associated with increased susceptibility to this disorder and coronary artery disease (CAD). We therefore undertook this study to determine the association between the occurrence of CAD and eNOS4 b/a polymorphism in Iranian patients. METHODS: We studied the 27 base pair tandem repeat polymorphism in intron4 of the endothelial nitric oxide synthase (eNOS) gene in 141 unrelated CAD patients with positive coronary angiograms and 159 age matched control subjects without a history of symptomatic CAD. The eNOS gene intron4a/b VNTR polymorphism was analyzed by polymerase chain reaction. The plasma lipids levels and other risk factors were also determined. RESULTS: The genotype frequencies for eNOS4b/b, eNOS4a/b and eNOS4a/a were 68.8, 29.1 and 2.1 per cent in CAD subjects, and 81, 18.4 and 0.6 per cent in control subjects, respectively. The genotype frequencies differed significantly (P<0.05) between the two groups. The frequency of the a allele was 16.7 per cent in CAD subjects and 9.8 per cent in control subjects and was significantly higher in the patients (P<0.05, Odds ratio=1.84). Plasma lipids, except HDL-C were also significantly increased in CAD group. INTERPRETATION & CONCLUSION: Though the genotype frequencies for eNOS4b/b, eNOS4a/b and eNOS4a/a, also 'a' allele frequency differed significantly between the CAD patients and controls, this polymorphism was not an independent risk factor for the development of CAD in Iranian patients. Further studies with larger samples need to be done to confirm these findings.