贵州汉族、苗族和布依族原发性高血压与载脂蛋白E基因单核苷酸多态性的关系

Relationship between essential hypertension and single nucleotide polymorphism of apolipoprotein E gene in Han,Miao and Buyi populations in Guizhou

目的 探讨载脂蛋白E(ApoE)基因单核苷酸多态性(SNP)与贵州汉族、苗族、布依族人群原发性高血压(EH)的关联性。方法 通过病例-对照研究方法,选取贵州雷山苗族、荔波布依族及贵阳汉族原发性高血压患者343例(苗族110例,布依族119例,汉族114例)和健康对照335例(苗族111例,布依族117例,汉族107例),并收集年龄、性别、身高、体质量、空腹血糖、总胆固醇、三酰甘油等临床资料和生化指标,采用t检验或χ^(2)检验比较两组临床资料与生化指标的差异。分别采用Sequenom MassARRAY和竞争性等位基因特异性PCR(KASP)基因分型技术对以上人群ApoE基因5个SNP位点(rs7259620、rs440446、rs769449、rs1065853、rs439401)和2个SNP位点(rs429358、rs7412)进行基因分型,采用logistic回归分析ApoE基因多态性与贵州人群EH的遗传关系。结果 在贵州苗族和布依族人群中,没有发现与EH关联的SNP位点。汉族人群rs439401等位基因及基因型在EH组和对照组的分布差异具有统计学意义(χ^(2)=6.438,P=0.011和χ^(2)=6.389,P=0.041)。与TT或TC基因型相比,CC基因型增加EH的患病风险(OR=2.164,95%CI 1.035~4.526,P=0.040)。与单倍型G-G-T(rs7259620-rs1065853-rs439401)相比,单倍型G-G-C降低汉族人群原发性高血压的患病风险(OR=0.465,95%CI 0.263~0.824,P=0.008)。多因子降维分析结果显示,rs440446,rs429358,rs7412对于苗族EH的发生具有交互作用(χ^(2)=10.012,P=0.002);rs7259620,rs1065853,rs439401对于布依族EH的发生具有交互作用(χ^(2)=3.972,P=0.046);rs7259620,rs440446,rs439401对于汉族EH的发生具有交互作用(χ^(2)=10.155,P=0.001)。结论 ApoE基因rs439401位点及单倍型G-G-C(rs7259620-rs1065853-rs439401)可能与贵州汉族EH的发生有关联。

Objectivee To investigate the correlation between single nucleotide polymorphism(SNP)of human apolipoprotein E(ApoE)gene and essential hypertension(EH)in Han,Miao and Buyi populations in Guizhou.Methods A case-control study was conducted.A total of 343 patients with EH(110 Miao,119 Buyi,114 Han)and 335 healthy controls(111 Miao,117 Buyi,107 Han)were selected from Leishan Miao,Libo Buyi and Guiyang Han populations in Guizhou.The clinical data and biochemical indicators including age,gender,height,weight,fasting blood glucose,cholesterol and triglyceride were collected.The t test or chi-square test was used to compare the differences of clinical data and biochemical indexes between the two groups.Sequenom MassARRAY and kompetitive allele specific PCR(KASP)were used to detect genotype of 5 SNPs(rs7259620,rs440446,rs769449,rs1065853,rs439401)and 2 SNPs(rs429358,rs7412)of ApoE gene respectively.Logistic regression was used to analyze the genetic relationship between ApoE gene polymorphisms and EH in Guizhou populations.Results In the Miao and Buyi populations in Guizhou,the correlation between EH and the SNP was not statistically significant.In the Han population,the distribution of rs439401 allele and genotype between EH group and control group was significantly different(χ^(2)=6.438,P=0.011;χ^(2)=6.389,P=0.041).Compared with the TT or TC genotype,the genotype CC increased the risk of EH(OR=2.164,95%CI 1.035-4.526,P=0.040).Compared with haplotype G-G-T(rs7259620-rs1065853-rs439401),haplotype GG-C reduced the risk of EH in Han population(OR=0.465,95%CI 0.263-0.824,P=0.008).Multi-factor dimensionality reduction analysis showed that rs440446,rs429358,rs7412 had the interaction effect on the occurrence of EH in Miao population(χ^(2)=10.012,P=0.002);rs7259620,rs1065853,rs439401 had the interaction effect on the occurrence of EH in Buyi population(χ^(2)=3.972,P=0.046);rs7259620,rs440446,rs439401 had the interaction effect on the occurrence of EH in Han population(χ^(2)=10.155,P=0.001.)C.onclusionThe rs439401 of ApoE gene and the haplotype G-G-C(rs7259620-rsl065853-rs439401)may be associated with the occurrence of EH in Guizhou Han population.