【摘要】 目的探讨中国北方人群HNF1B基因位点rs4430796单核苷酸多态性(SNP)与冠心病及其共病的相关性。方法采用病例对照研究,入选2016年2~12月于北京医院心内科和内分泌科就诊的冠心病患者160例、2型糖尿病患者126例、冠心病合并2型糖尿病患者175例,及健康对照者238名。采用高分辨率熔解曲线分析和直接测序的方法检测HNF1B基因位点rs4430796多态性,同时测定血清中尿酸(UA)、总胆固醇(TC)、三酰甘油(TG)、低密度脂蛋白胆固醇(LDL-C)和高密度脂蛋白胆固醇(HDL-C)水平,评估rs4430796多态性与上述生物标志物的相关性。结果与健康对照组比较,冠心病合并2型糖尿病组HNF1B基因rs4430796在基因型(P=0.005)、等位基因(OR=1.50,95%CI:1.05~2.13,P=0.026)、显性模型(OR=1.83,95%CI:1.23~2.72,P=0.003)、隐性模型(OR=2.07,95%CI:1.07~3.98,P=0.027)、加性模型(OR=2.53,95%CI:1.29~4.98,P=0.006)差异均有统计学意义。与野生型(AA)比较,冠心病组携带rs4430796 G突变位点(GG+AG)的患者体质指数增高,2型糖尿病组携带rs4430796 G突变位点(GG+AG)的患者尿酸增高,冠心病合并2型糖尿组携带rs4430796 G突变位点(GG+AG)的患者HDL-C较低(均为P<0.05)。结论HNF1B基因位点rs4430796多态性与冠心病合并2型糖尿病相关,可能通过代谢因素参与冠心病及其共病的发生。更多还原

【Abstract】 Objective To investigate the association between single nucleotide polymorphisms(SNPs) of hepatocyte nuclear factor 1β(HNF1 B) gene locus rs4430796 and coronary artery disease(CAD)and type 2 diabetes(T2 DM) comorbidity in northern China. Methods We enrolled CAD(n = 160),T2 DM(n = 126),CAD + T2 DM(n = 175) patients and control subjects(n = 238) from February 2016 to December 2016 in the department of cardiology and endocrinology in Beijing Hospital. The genotype of HNF1 B rs4430796 was detected by high resolution melt(HRM) and sanger sequencing. A case control study was conducted to evaluate the relationship between HNF1 B rs4430796 polymorphism and risk of CAD,T2 DM,CAD + T2 DM. The clinical characteristics,serum uric acid(UA),total cholesterol(TC),triglyceride(TG) and low-density lipoprotein cholesterol(LDL-C) and high-density lipoprotein cholesterol(HDL-C) levels were used to assess the association to explore the genotype-phenotype relationship. Results There were significant differences in the distribution of genotype frequencies(P = 0. 005),allele frequencies(OR = 1. 50,95% CI: 1. 05-2. 13,P = 0. 026),dominant model(OR = 1. 83,95% CI: 1. 23-2. 72,P = 0. 003),recessive model(OR = 2. 07,95% CI: 1. 07-3. 98,P = 0. 027) and additive model(OR = 2. 53,95% CI: 1. 29-4. 98,P =0. 006) between the CAD + T2 DM patients and controls in HNF1 B gene rs4430796 polymorphism. Compared with wild-type(AA) patients,the body mass index levels were significantly lower in CAD patients with rs4430796 G mutation site(GG + AG); the UA levels were significantly higher in GG + AG genotype than in AA genotype in T2 DM patients; the HDL-C levels were significantly lower in GG + AG genotype than in AA genotype in CAD + T2 DM patients(all P < 0. 05). Conclusions The results show that HNF1 B gene rs4430796 polymorphism is associated with susceptibility to CAD + T2 DM in the Chinese population by involving metabolic disorder.更多还原