Association Study On Susceptibility Genes Of Coronary Heart Disease In Chinese Han Population

Background: Coronary artery disease(CAD) is one of the leading causes of death and loss of disability-adjusted life years in both developed and developing countries. In China, the World Health Organization estimated that more than 700,000 people die from CAD each year. Coronary heart disease(CHD), the most serious clinical manifestation of CAD, is the leading cause of death worldwide. CHD is a complex disease characterized by the inheritance of multiple genetic variants acting in concert with environmental factors to promote the disease state. Although epidemiological studies have identified many risk factors for coronary heart disease, including plasma lipid concentrations, blood pressure,smoking, diabetes and markers of inflammation, a causal role has been proven only for some(for example, low-density lipoprotein(LDL)cholesterol and blood pressure) primarily through randomized clinical trials of drug therapy directed at the risk factor. Twin and family studies have demonstrated that a significant proportion(40–50%) of susceptibility to CHD is heritable A previous linkage study and candidate gene study have identified genetic factors predisposing to CHD. However, the results of CHD genetic studies have not been very satisfactory.Recently, GWAS have proven to be a powerful tool to identify susceptibility genes for common diseases. To date, genome-wide association(GWA) studies in Caucasians identified multiple single nucleotide polymorphisms(SNPs) associated with coronary artery disease. However, most of these GWASs were conducted in Caucasian population.Besides the GWASs finished by our team, few large GWASs are performed in Chinese Han population. As is known, great difference in the genetic structure existed in between Chinese Han population and Caucasian population. So, are the established CHD susceptibility loci also associated with CHD in Chinese Han population? To date,there is not a study on these problems. If they are fully understood, it’s helpful to reveal the pathogenesis of CHD and then for drug research and development, CHD prevention and diagnosis, and individualized treatment. We have a large sample size and technical advantages on genetic research, which enable us to complete the study successfully.Objective: To verified the association between coronary heart disease(CHD) and the susceptibility SNPs(Single Nucleotide Polymorphism) in Chinese Han population.Among these previously identified SNPs, we selected five(rs17114036, rs9369640,rs515135, rs579459 and rs8055236) due to the relatively high minor allele frequencies in Chinese individuals and tested the associations of the SNPs with CHD in a Chinese population.Methods: 1)We performed a case-controlled association study on a cohort of 1008 CHD patients and 545 unrelated controls from a Chinese population. Genotyping of the5 SNPs was performed using a sequenom Mass array system. 2)A thorough literature search about studies on the relationship between the polymorphism of rs2383206 and rs2383207 loci and CHD was performed among Chinese Biomedical literature Database(CBM),Chinese knowledge Internet(CNKI) and pubmed. Rev Man5.0 software was used to perform the meta-analysis on those valid studies. Results: 1)A novel significant association was found between rs515135 in the APOB gene and coronary heart disease(OR=1.48, 95% CI 1.138-1.925, P=0.00333), However, no statistical associations were found between rs515135 and other clinical characteristics, including blood pressure,smoking, and diabetes. rs17114036 、 rs9369640 and rs579459 showed only a trend association with coronary artery disease in this study. 2)Using stratified analysis, we found that rs579459 is strongly associated with severe coronary heart disease, and similar associations were not observed for the other SNPs.3) The polymorphism of rs2383206 and rs2383207 loci were significant association with CHD in Chinese Han population.Conclusion: 1)rs515135 is associated with the susceptibility of coronary heart disease,and it located in the APOB gene, which might be involved in the pathogenesis of coronary heart disease. 2) In addition, our study also showed that genetic factors,specifically rs579459, may affect coronary heart disease severity. 3) 9p21 rs2383206 and rs2383207 loci genotype may be the protection genotype of CHD.