Association Between MVK Rs2287218 SNP And The Risk Of Coronary Heart Disease And Ischemic Stroke:a Case-control Study

Objective:Several recent genome-wide association studies(GWASes)in different populations have indentified the MVK genetic variants influencing serum lipid levels,but these results are not entirely consistent.It is still unclear whether the loci indentified exert the similar effect on the susceptibility of coronary heart disease(CHD)or ischemic stroke(IS)in a Southern Chinese Han population.Therefore,the present study is undertaken to expand our understanding of the association between the rs2287218 single nucleotide polymorphism(SNP)and serum lipid levels,and the susceptibility of CHD and IS in a Southern Chinese Han population.Methods:According to the experimental purpose,the subjects were divided into control group and experimental groups.Among the numerous study subjects,1,138 unrelated subjects(583 patients with CHD,555 patients with IS and 626 healthy subjects as control groups)were finally selected by inclusion and exclusion.General clinical data were obtained through questionnaire survey and physical examinations.Blood samples of the subjects were taken for blood lipid determination,DNA extraction and genotype determination.MVK rs2287218 genotypes were obtained through Snapshot technology analysis.Results:In our study subjects,the genotype distribution and allele frequency of the rs2287218 SNP in the CHD or the IS groups and the control group were significant difference(P<0.013 and P<0.01,respectively).The T allele carriers had higher risk of CHD and IS than the T allele non-carriers(CHD:OR=1.674,P=0.001 for CT/TT vs CC;OR=1.595,P<0.001 for T vs C allele;IS:OR=1.890,P=0.001 for CT/TT vs CC;OR=1.829,P<0.001 for T vs C allele).In healthy controls,rs2287218 SNP was closely related to high-density lipoprotein cholesterol(HDL-C)levels,in which the subjects with CT/TT genotypes had lower HDL-C concentrations than the subjects with CC genotype(P=0.013).After adjusting for environmental factors,the corresponding genetic model showed that rs2287218 SNP genotypes were associated with CHD and IS(P<0.05).In addition,in the stratified analysis,the increased risks of CHD and IS in subjects with the CT and TT genotypes were mainly observed in females,age>60 years,BMI<24kg/m~2,nonsmokers and nondrinkers(P<0.05).Significant interactions between rs2287218 SNP and females,nonsmokers and nondrinkers to increase the risk of CHD and IS were also observed(P<0.05).Multivariate analysis showed that the known common factors,such as smoking habit,BMI?24kg/m~2,hypertension,hyperlipidemia and the TT/CT genotypes were dependently associated with CHD risk.Meanwhile,the occurrence of IS was positively correlated with cigarette,high BMI,hypertension and the TT/CT genotypes.However,both CHD and IS were negatively correlated with rs2287218 CC genotype and alcohol consumption.Conclusions:MVK rs2287218 SNP is likely to increase the risk of CHD and IS by decreasing serum HDL-C levels in our study populations.In addition,rs2287218 SNP may interact with some environmental factors,which may have a certain effect on the risk of CHD and IS.