title: Association of ARHGEF11 R1467H polymorphism with risk for type 2 diabetes mellitus and insulin resistance in Chinese population.
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.
authors.affiliation: Department of Endocrinology, Gansu Provincial People's Hospital, and First Clinical Medical School of Lanzhou University, 204 West Donggang Road, Lanzhou, 730000, Gansu, People's Republic of China. liujingwelcome@126.com
authors.forename: Jing
authors.initials: J
authors.lastname: Liu
authors.forename: Xiaohui
authors.initials: X
authors.lastname: Chen
authors.forename: Qian
authors.initials: Q
authors.lastname: Guo
authors.forename: Xiaoqin
authors.initials: X
authors.lastname: Ma
authors.forename: Junqiang
authors.initials: J
authors.lastname: Zhang
authors.forename: Xiaofeng
authors.initials: X
authors.lastname: Huang
authors.forename: Xiaohui
authors.initials: X
authors.lastname: Zhang
authors.forename: Shulan
authors.initials: S
authors.lastname: Zhang
mesh_terms: D000367:Age Factors; D044466:Asian People / Q000235:genetics*; D001483:Base Sequence; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics*; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D055106:Genome-Wide Association Study; D005838:Genotype; D020662:Guanine Nucleotide Exchange Factors / Q000235:genetics*; D006801:Humans; D007333:Insulin Resistance / Q000235:genetics*; D008969:Molecular Sequence Data; D020125:Mutation, Missense / Q000235:genetics; D012150:Polymorphism, Restriction Fragment Length; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D064067:Rho Guanine Nucleotide Exchange Factors; D017422:Sequence Analysis, DNA; D012737:Sex Factors
chemical_list: C577234:ARHGEF11 protein, human; D020662:Guanine Nucleotide Exchange Factors; D064067:Rho Guanine Nucleotide Exchange Factors