The Study Of Tumor Necrosis Factor-α Gene Polymorphisms And Risk Of Coronary Heart Disease

Coronary heart disease(CHD) is an complicated disease that can threaten people's health. The pathological mechanism of CHD is complex, although hypercholesterolemia is important in approximately 50 percent of patients with cardiovascular disease, other factors need to be taken into consideration. It's a reciprocal result of gene and circumstance. Inflammatory is very important in the formation of the lesion, influence the whole process. Tumor necrosis factor-α(TNF-α) is a proinflammatory cytokine with pleiotropic biological effects, and may contribute to the progression of atheroma by augmenting the inflammatory response. The object of the study was to type the single nucleotide polymorphisms(SNPs) in the promoter of TNF-α at-1031, -863, -857, -238 locus in Chinese han population of Hubei and investigated the correlation between TNF-α polymorphisms and CHD.Some studies in this area have been published before, but there are bias in the results. We first use PCR-RFLP methods to type the single nucleotide polymorphisms (SNPs) in the promoter of TNF-α of 236 cases in Chinese han population of Hubei. We compare the frequency of the genotypes and alleles. In addition, TNF-α -238,-857,-863 and -1031 haplotypes were assigned and compared, the results are:1. the polymorphism of TNF-α -238,-857,-863 and -1031 exist in Chinese han population of Hubei;2. the SNPs frequency are variable among different population;3. the TNF-α -863 CC genotype showed slight, but significant, correlation with CHD. The frequency of TNF-α -863C allele in CHD is higher, A allele is lower than in the controls, which seems to show -863C is a risk factor in the developing phases of the atherosclerotic process [P=0.036;OR=1.812(1.035 ~ 3.170)]. And this association achieved significance at P=0.05 when we used multivariable logistic regression analysis for risks of CHD[P=0.0235, OR=2.218,(1.113~4.420)];4. there are no different of other 3 SNPs in two groups;5. the GCCT haplotype was the most common in both CHD patients and controls. There were no significant difference of the haplotypesdistribution between two groups and the difference of haplotype GCAT with only one mutation at -863 site between two groups has no significant difference.There were some researches about TNF-a polymorphism and diseases before. Its correlation with CHD has been reported in other population. The study was the first to report the SNPs of TNF-a-103K-863^857>-238 in Chinese hanpopulation of Hubei. We hope to provide information for further study and the preliminary findings of our study suggest that TNF-a -863C may be a risk factor for CHD, other genetic variations are unlikely to play a major role in susceptibility to and perhaps prognosis in CHD.