HLA-DRB1基因多态性与原发性高血压发病的关联性分析

目的:探讨HLA-DRB1基因rs2308765、rs9269186和rs3135388位点多态性及环境因素与原发性高血压(EH)的关系,阐明HLA-DRB1基因与EH发病的关联性。方法:采用病例-对照研究设计,选取161例EH患者为病例组,147名健康人为对照组。收集EH相关因素,并应用PCR-LDR技术进行HLA-DRB1基因rs2308765、rs9269186和rs3135388 3个位点的多态性检测。结果:病例组患者体质量指数(BMI)、腰围(WC)、血糖(BG)、总胆固醇(TC)、甘油三酯(TG)和低密度脂蛋白胆固醇(LDL-C)水平均明显高于对照组(P<0.05或P<0.01),而高密度脂蛋白胆固醇(HDL-C)水平明显低于对照组(P<0.01)。调整混杂因素后Logistic回归分析,高BMI(OR=1.140,95%CI:1.040~1.249)和高TG(OR=1.215,95%CI:1.016~1.452)是EH的独立危险因素。病例组患者rs2308765位点GG基因型频数和G等位基因频数均明显低于对照组(χ²=4.666,P=0.031;χ²=4.485,P=0.034);病例组患者rs3135388位点CC和CT基因型频数及rs9269186位点CC、CG和GG基因型频数与对照组比较差异均无统计学意义(P>0.05),C和T等位基因频数、C和G等位基因频数比较差异均无统计学意义(P>0.05)。BMI、TG、TC和HDL-C 4个环境因素中,除rs2308765位点多态性与TG存在交互作用(P<0.05)外,rs2308765位点多态性与其他3个环境因素无交互作用(P>0.05);rs3135388和rs9269186位点多态性与4个环境因素均无交互作用(P>0.05)。结论:BMI、TG水平和HLA-DRB1基因rs2308765位点多态性与EH存在关联,高BMI和高TG是EH的危险因素,rs2308765 位点G→T突变可能是EH的危险因素。

Association between HLA-DRB1 gene polymorphisms and essential hypertension

Objective To explore the association between HLA-DRB1 gene rs2308765, rs9269186 and rs3135388 polymorphisms and essential hypertension(EH), and to clarify the association between single nucleotide polymorphisms(SNPs) of HLA-DRB1 gene and EH. Methods Using case-control study design, 161 patients with EH were recruited in case group and 147 healthy persons were selected as control group.The related factors of EH were collected and the polymorphisms of HLA-DRB1 rs2308765, rs9269186 and rs3135388 sites were detected with PCR-LDR. Results The body mass index(BMI), waist circuit(WC), blood glucose(BG), total cholesterol(TC), triglyceride(TG) and low density lipoprotein cholsterol (LDL-C) levels of the patents in case group were significantly higher than those in control group(P<0.05 or P<0.01), while the level of high density lipoprotein cholesterol (HDL-C) was significantly lower than that in control group(P<0.01).After the potential confounders in the model of Logistic regress were adjusted, the high BMI (OR=1.140, 95%CI:1.040-1.249)and TG (OR=1.215, 95%CI:1.016-1.452) were detected as the independent risk factors of EH.The frequency of the genotype GG and the frequency of G allele of rs2308765 site in case group were significantly lower than those in control group(χ²=4.666, P=0.031;χ²=4.485, P=0.034).The distribution of genotypic and allelic frequencies of rs3135388 and rs9269186 sites were not significantly different between case group and control group(P>0.05).Among the four environmental factors, such as BMI, TG, TC and HDL-C, only rs2308765 polymorphisms had interaction with TG(P<0.05). Conclusion The BMI, TG and SNPs of rs2308765 site of HLA-DRB1 gene are associated with EH.High BMI and high TG are the risk factors of EH, and rs2308765 G/T mutation might be the risk factor of EH.