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

Author:
Liu, Jing, Chen, Xiaohui, Guo, Qian, Ma, Xiaoqin, Zhang, Junqiang, Huang, Xiaofeng, Zhang, Xiaohui, Zhang, Shulan
Source:
Molecular biology reports 2011 v.38 no.4 pp. 2499-2505
ISSN:
0301-4851
Subject:
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
Abstract:
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.
Agid:
381998