Association Between Single Nucleotide Polymorphisms On Chromosome11q23.3and Myocardial Infarction In The Chinese Han Population

Myocardial infarction (MI) is a serious consequence of coronary arterydisease (CAD). MI is a complex and multifactorial disorder that results from thecomplex interaction between genetics and environmental factors. Recentgenome-wide association studies (GWAS) have identified manysingle-nucleotide polymorphisms (SNPs) associated with CAD and MI acrossdiverse ethnic groups. This association can be used as an important predictivetool to determine an individual’s predisposition to heart disease. Thus，validation of these loci in different ethnic populations is important fordetermining their clinical relevance across diverse populations.Objective: To examine the association between commonly and recentlyidentified SNPs associated with risk of MI within the Chinese Han population.Methods: According to predefined criteria，549Chinese patients withacute MI and551Chinese subjects (controls) without a history of coronaryartery disease (CAD) were selected for the study. Genomic DNA was extractedfrom peripheral blood of subjects using a phenol-chloroform purificationmethod. Three prevalent single nucleotide polymorphisms (SNPs;rs1412444(LIPA)， rs662799(APOA5) and rs964184(ZNF259)) associated with CAD and MI， in other ethnic populations， were selected for sequence andassociation analyses within blood DNA of the Chinese Han population.SNPStats was used to estimate the odds ratios (ORs), their corresponding95%confidence intervals (CIs), and p values. Confounding factors was adjusted andBonferroni correction was also done.Results: Only two SNPs， rs662799(APOA5) and rs964184(ZNF259)，were associated with risk of MI in the Chinese Han population. After adjustingconfounding factors and using Bonferroni correction methods， significantdifferences in the association of these two SNPs (rs662799(OR=1.39,95%CI=1.09-1.78, p=0.0228) and rs964184(OR=1.52,95%CI=1.16-1.98, p=0.0060)) between Chinese patients with MI versus controls were revealed.Strong linkage disequilibrium were observed between rs662799and rs964184(D’=0.959and r2=0.652for MI group; D’=0.955and r2=0.658for control group).Detailed examinations of the haplotypes composed of SNPs, rs662799andrs964184, revealed that the GG haplotype (frequency=21.4%), which consists ofthe minor allele of each marker, was significantly associated with MI in theChinese Han population after adjusting for conventional risk factors(OR=1.50,95%CI=1.14-1.97and p=0.0034). Further statistic analysis on part of theconfounding factors was done for further study of the pathogenesis of thisassociation.The result indicated rs662799and rs964184were also associatedwith triglyceride in the Chinese Han population. After adjusting confoundingfactors and using Bonferroni correction methods， significant differences in the association of these two SNPs (rs662799(Difference=0.09,95%CI=0.04-0.14,p=0.0015) and rs964184(Difference=0.07,95%CI=0.01-0.12, p=0.0042))between Chinese patients with MI versus controls were revealed.Conclusion: We identified a significant association between two SNPs(rs964184and rs662799) on chromosome11q23.3and MI risk in the ChineseHan population. The related pathogenic gene may be associated withtriglycerides. The results extend their clinical relevance to predicting the risk ofMI in diverse ethnic populations and offer some data for the study on the geneticmechanisms of MI.