| Objective: To investigate the distribution of the single nucleitide polymorphism in exon 7 (G894T) and the insert/deletion polymorphism of variable number of tandem repeat in intron 4 (4a/b) of the endothelial nitric oxide synthase (eNOS) in the Han population in Tianjin, and to assess if it is possible weather G894T or 4a/b polymorphism of the gene is associated with coronary heart disease (CHD) in type 2 diabetics.Methods: A total of 291 Han peoplel was involved in the study. The participants included of 119 control subjects (67 male, 52 female, average age was 50.97 ±7.71) as group A, 80 type 2 diabetic patients (39 male, 41 female, average age was 51.95 ±10.03) as group B, 92 type 2 diabetic patients with coronary heart disease (47 male, 45 female, average age was 61.13 ± 9.40) as group C. Type 2 diabetic patients were recruited among those regularly attending the Diatetes Clinic of the TianJin General Hospital. People who underwent a check-up examination in the same hospital during the same period of time (between July 200land July 2002) were enrolled as random population control. The participants were genetically unrelated and were all living in Tianjin. Genomic DNA was extracted from anticoagulant whole blood. The G894T polymorphism was determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis. The 4a/b polymorphism was determined by polymerase chain reaction-variable number of tandem repeat (PCR-VNTR) analysis.Results: (1) The prevalence of the eNOS alleles and genotypes in each group were consistent with Hardy-Weinberg equilibrium law. (2) The frequency of theallele 4a or T of the eNOS gene in the Han people was 9.66%, which was lower than that in Caucasian (P<0.01) and was similar with that in Janpanese. (3) The genotype frequency of G894T polymorphism of the eNOS gene in group A was 82.35% for GG, 15.97% for GT, and 1.68% for TT. It was respectively 78.75%, 21.25%, and 0.00% in group B; and was 63.04%, 32.60%, and 4.35% in group C. There were significant differences in genotype and allele frequencies of G894T polymorphism among three groups (P<0.01), among which group C seemed to have higher frequencies of allele T and GT/TT genotype than that in group A and B. Between the two, the frequency was similar. (4) The genotype frequency of 4a/b polymorphism of the eNOS gene in group A was 80.67% for 4b/b, 19.33% for 4b/a, and 0.00% for 4a/a. It was 83.75%, 16.25%, and 0.00% respectively in group B; and 77.17%, 21.74%, and 1.09% in group C. The statistics showed that there was no significant difference of the genotype frequency among three groups. (5) Analysis showed that the more risk factors T2DM patients had, the higher the frequency of allele T was. (6) Logistic regression analysis showed that G894T polymorphism of the eNOS gene, smoking, BMI, age and serum uric acid level were indepengdent variables for CHD in type 2 diabetics. In comparison with the GG genotype, the odds ratio (95% confidence interval) for CHD in T2DM associated with the genotype carrying of allele T (GT/TT) was 3.293(1.458,7.440). (7) The blood pressure was significantly elevated in the hyperinsulinirnic carriers of allele T.Conclusions: The data from Madel's genetics study showed that there was G894T and 4a/b polymorphism of the eNOS gene in the Han population of Tianjin. The G894T polymorphism was significantly associated with CHD in type 2 diabetics, and allele T was the independent risk factor of type 2 diabetic patients complicated with CHD. No significant association was observed hi the comparison of either genotype distribution or allele frequencies of the 4a/b polymorphism with CHD in type 2 diabetics. The allelic variation (G894T) of the eNOS gene locus in conjunction with insulin-resistance status maybe one factorcontributing to the predisposition to hypertension, and make the function of the endothelial dependent vasodilation impaired. |
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