Association of hepatocyte nuclear factor 1β gene polymorphism with coronary artery disease and type 2 diabetes comorbidity

Abstract

Objective To investigate the association between single nucleotide polymorphisms(SNPs)of hepatocyte nuclear factor 1β(HNF1B)gene locus rs4430796 and coronary artery disease(CAD)and type 2 diabetes(T2DM)comorbidity in northern China. Methods We enrolled CAD(n=160), T2DM(n=126), CAD+ T2DM(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 HNF1B rs4430796 was detected by high resolution melt(HRM)and sanger sequencing.A case control study was conducted to evaluate the relationship between HNF1B rs4430796 polymorphism and risk of CAD, T2DM, CAD+ T2DM.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+ T2DM patients and controls in HNF1B 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 T2DM patients; the HDL-C levels were significantly lower in GG+ AG genotype than in AA genotype in CAD+ T2DM patients(all P<0.05). Conclusions The results show that HNF1B gene rs4430796 polymorphism is associated with susceptibility to CAD+ T2DM in the Chinese population by involving metabolic disorder. Key words: Hepatocyte nuclear factor 1-beta; Coronary artery disease; Diabetes mellitus, type 2; Comorbidity; Gene polymorphism