Relationship Between Nitric Oxide Synthase Interleukin-6 Gene Polymorphism And Coronary Heart Disease In Young People

Objective: Endothelial nitric oxide synthase(e NOS) and IL-6 has been shown to be associated with the occurrence of coronary heart disease in the present study. This study was to investigate the relationship between e NOS gene G894 T, T786 C, 4b/a, IL-6 174G/C, 572C/G, 597G/A polymorphism and coronary heart disease in young patients.Methods: 156 young patients with coronary heart disease who were admitted to our hospital from August 2013 to May 2015 were selected. CHD diagnosis was in line with the CHD Chinese Medical Association diagnostic criteria. All patients were treated by coronary angiography. There were 132 males and 24 females. The age range was 27-40(34.2±3.7) years. In the control group, 152 hospitalised patients(including 130 males and 22 females The age range was 29-40(35.7±2.6) years) were selected in the same period. The physical examination and laboratory tests were not found to be significantly abnormal in the control group. There was no consanguinity between the subjects selected in either groups. Age and gender difference was not statistically significant. The e NOS and IL-6 gene polymorphism were analyzed by polymerase chain reaction- restriction fragment length polymorphism assay(PCR-RFLP).Results: 1. The genotype distribution of e NOS and IL-6 gene polymorphism in our study population did not deviate significantly from the Hardy-Weinberg distribution, they have a group representative. For G894 T, Although the frequencies of e NOS GT and TT phenotypes were higher in the premature CHD group, this difference did not reach statistical significance(?2:5.46, P=0.065). The distribution of genotypes calculated by direct counting of “G” and “T” alleles revealed statistically higher frequency of allele “T” in the premature CHD group(?2: 4.715, P=0.03). Although the frequencies of e NOS T786 C TC and CC phenotypes were higher in the premature CHD group, this difference did not reach statistical significance(?2:5.111, P = 0.078). The distribution of genotypes calculated by direct counting of “T” and “C” alleles revealed statistically higher frequency of allele “C” in the premature CHD group(?2: 4.709, P = 0.03). The distribution of genotypes calculated by direct counting of “G” and “T” alleles revealed statistically higher frequency of allele “T” in the premature CHD group(?2: 4.715, P=0.03). The differences of 4a/4a, 4a/4b, 4b/4b, “a”, “b” frequency between the CHD and control group did not reach statistical significance. Elevated levels of hs-CRP?LDL-C and triglycerides were the only independent predictors of premature CHD in the study population. 2. IL-6 174G/C, genotype CC was not found in the two groups. The differences of GG, GC, “G”, “C” frequency between the CHD and control group did not reach statistical significance. IL-6 572C/G, The differences of CC, CG, GG, “C”, “G” frequency between the CHD and control group reach statistical significance. IL-6 597G/A only genotype GG was found in the two groups. 3. For G894 T gene polymorphisms, genotype GT,(GT+TT) and the T allele and CHD, there is a statistically significant correlation between susceptibility(respectively, OR=1.41,95%CI=(1.03-2.57), P=0.024; OR=1.46, 95%CI=(1.02-2.53), P=0.026; OR=1.35, 95%CI=(1.06-2.14), P=0.025) and on the risk factors of age, sex, and other adjustments, for each genotype and allele T relationship between CHD and were not statistically significant, but genotype(GT+TT), though not sure there is a statistically significant correlation and CHD, but still there are some statistically significant trends. For T786 C gene polymorphism, univariate Logistic analysis found that apart from the genotype CC, and TC genotypes,(TC+CC) and allele C there were significant associations with CHD(respectively, OR=1.62, 95%CI=(1.05-2.62), P=0.029; OR=1.54, 95%CI=(1.03-2.38), P=0.014; OR=1.51, 95%CI=(1.17-2.13), P=0.027); after adjusting for other risk factors, genotypes TC and(TC+CC), though not sure there is a statistically significant correlation with CHD, but close to the statistical differences.(OR=1.54, 95%CI=(0.80-2.75), P=0.083; OR=1.39,95%CI=(0.78-2.56), P=0.076). e NOS gene 4b/a polymorphism, univariate Logistic analysis and multivariate Logistic analysis found that there were no significant associations with CHD. 4. IL-6 174G/C polymorphism, univariate Logistic analysis and multivariate Logistic analysis found that there were no significant associations with CHD. IL-6 572C/G, univariate Logistic analysis and multivariate Logistic analysis found that there were significant associations between GG genotype, “G” allele and CHD. 5. e NOS G894 T, 4b/a polymorphism are not associated with the distribution of affected vessel and Gensini scores. T786 C polymorphism is associated with the distribution of affected vessel but not associated with Gensini scores. 6. IL-6 174G/C polymorphism are not associated with the distribution of affected vessel and Gensini scores. IL-6 572C/G polymorphism are not associated with the distribution Gensini scores, the association between IL-6 572C/G polymorphism and Gensini scores is close to statistical significance. 7. Multivariate Logistic analysis found that the haplotype G-C-4b and G-G-G are significantly associated with CHD(OR=6.87,95%CI=(1.33,29.6),P=0.029; OR=2.15,95%CI=(0.97,4.86),P=0.037, respectively).Conclusion: In the studied Henan Han young population, 1. e NOS gene 4b/a polymorphism is not a risk factor for CHD. T786 Cand G894T are risk factor for CHD, but not a independent risk factor. IL-6 572C/G is an independent risk factor for CHD. 2. e NOS gene T786 polymorphism is associated with the distribution of affected vessel. The association between IL-6 572C/G polymorphism and Gensini scores is close to statistical significance. 3. The haplotype G-C-4b and G-G-G are independent risk factor CHD in young population.