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Association of ARHGEF11 R1467H polymorphism with risk for type 2 diabetes mellitus and insulin resistance in Chinese population

Liu, Jing, Chen, Xiaohui, Guo, Qian, Ma, Xiaoqin, Zhang, Junqiang, Huang, Xiaofeng, Zhang, Xiaohui, Zhang, Shulan
Molecular biology reports 2011 v.38 no.4 pp. 2499-2505
G-proteins, body mass index, chromosomes, gender, genes, genotype, guanosinetriphosphatase, humans, insulin resistance, insulin secretion, noninsulin-dependent diabetes mellitus, patients, risk, sequence analysis, signal transduction
The human Rho guanine nucleotide exchange factor 11 (ARHGEF11), located on chromosome 1q21, is an activator of Rho GTPases involved in G protein signaling pathway known to regulate insulin secretion and action. The aim of our study was to evaluate the relationship between the previously reported R1467H G/A variant in ARHGEF11 and risk of type 2 diabetes mellitus (T2DM) and insulin resistance as well as metabolic traits in a Chinese population. We genotyped R1467H G/A polymorphism in 311 patients with T2DM and 328 control subjects in a Chinese population, using a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) protocol and DNA sequencing methods. The genotype and allele distributions of the R1467H G/A polymorphism were significantly different between the T2DM group and the normal control group (P = 0.024, 0.018, respectively) and we also found that the A allele carriers (GA + AA genotype) had markedly higher risk of T2DM as compared with the wild-type GG genotype after adjustment for gender, age, and BMI (OR = 1.578, 95% CI 1.126-2.212, P = 0.008). Moreover, in the T2DM group the A allele carriers had higher FPG, FINS, and HOMA-IR than that of the GG homozygote (P = 0.015, 0.029, and 0.007, respectively). FPG and HOMA-IR levels were also significantly increased from A allele carriers to GG homozygote in the control group (P = 0.017, 0.012, respectively). Our investigation suggests that the R1467H polymorphism of ARHGEF11 gene may contribute to susceptibility to T2DM and insulin resistance in a Chinese population.