Association Of ARHGEF11 Gene R1467H Polymorphism With Type2 Diabetes Mellitus In Gansu Hui And Han Population

Objectives The aim of our study was to investigate the distribution and difference of ARHGEF11 gene R1467H polymorphism in Hui and Han population in Gansu province. To evaluate the relationship between the R1467H polymorphism in ARHGEF11 and risk of type 2 diabetes mellitus (T2DM) and insulin resistance in Hui and Han population in Gansu province.Methods We genotyped R1467H polymorphism in 117 patients with T2DM and 104 control subjects in Gansu Hui population and 149 patients with T2DM and 114 control subjects in Gansu Han population, using a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) protocol and DNA sequencing methods. The frequencies of genotypes and alleles at the site were compared between the T2DM and control groups. Total cholesterol (TC), triglyceride (TG), high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C) and fasting blood glucose levels were determined by automatic biochemistry analyzer. Glycosylated hemoglobin (HbAlc) value was determined by HbAlc analyzer. Fasting insulin concentration was measured using insulin radioimmunoassay kit. At the same time, we measured the height, weight, waist circumference, hip circumference, blood pressure. The body mass index (BMI), waist hip ratio (WHR) and insulin resistance index (HOMA-IR) were computed.Results (1) There was no significant difference in distribution of genotype and allele in R1467H polymorphism between T2DM and NC in Hui and Han population of Gansu province. (P>0.05); (2) Genotype frequencies of GG, GA, AA were 61.1%, 35.6%,3.3%in T2DM group and 75.4%,21.1%,3.5%in NC group, allele frequencies of G, A were 78.9%,21.1%in T2DM group and 86.0%,14.0%in NC group in Han population. Genotype frequencies of GG, GA, AA were50.4%,43.6%, 6.0%in T2DM group and 66.3%,28.8%,4.8%in NC group, allele frequencies of G, A were 72.2%,27.8%in T2DM group and 80.8%,19.2%in NC group in Hui population. There was a significant difference in distribution of genotype and allele in R1467H polymorphism between T2DM and NC in Han and Hui population; (3) The relative risk of GA genotype in the T2DM of Han population was significantly higher than GG genotype (OR=2.087,95% CI:1.186-3.673, P= 0.010). And A allele was associated with increased risk of T2DM (OR= 1.642,95% CI:1.031-2.616, P= 0.036). The relative risk of GA genotype in the T2DM of Hui population was significantly higher than GG genotype (OR,1.988; 95% CI,1.125-3.513, P= 0.017). And A allele was associated with increased risk of T2DM (OR,1.6.15; 95%CI, 1.032-2.528, P= 0.035); (4) In Han population, the levels of FPG, FINS and HOMA-IR in the type 2 diabetes group of Han population were higher in A allele carriers (GA+AA genotype) than those of GG genotype (all P< 0.05). The level of FPG in the NC group was significantly higher in genotypes with allele A than in GG genotype (P< 0.05). In Hui population, the level of FPG in the type 2 diabetes group was significantly higher in GA+AA genotype than in GG genotype (P= 0.002). In the NC group, the subjects carrying GA, AA genotype had the significant increased levels of WHR and LDL-C (P< 0.05).Conclusion There was no significant difference in distribution of ARHGEF11 R1467H polymorphism between T2DM and NC in Hui and Han population of Gansu province. Our investigation suggests that the R1467H polymorphism of ARHGEF11 gene may contribute to susceptibility to T2DM and insulin resistance in Han population in Gansu province. Moreover, the SNP was likely related to increased risk of T2DM, obesity and dyslipidemia in Hui population in Gansu province.