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Associations of common polymorphisms in GCKR with type 2 diabetes and related traits in a Han Chinese population: a case-control study.

ABSTRACT: BACKGROUND: Several studies have shown that variants in the glucokinase regulatory protein gene (GCKR) were associated with type 2 diabetes and dyslipidemia. The purpose of this study was to examine whether tag single nucleotide polymorphisms (SNPs) in the GCKR region were associated with type 2 diabetes and related traits in a Han Chinese population and to identify the potential mechanisms underlying these associations. METHODS: We investigated the association of polymorphisms in the GCKR gene with type 2 diabetes by employing a case-control study design (1118 cases and 1161 controls). Four tag SNPs (rs8179206, rs2293572, rs3817588 and rs780094) with pairwise r2>0.8 and minor allele frequency>0.05 across the GCKR gene and its flanking regions were studied and haplotypes were constructed. Genotyping was performed by matrix-assisted laser desorption/ionization time-of-flight mass spectroscopy using a MassARRAY platform. RESULTS: The G alleles of GCKR rs3817588 and rs780094 were associated with an increased risk of type 2 diabetes after adjustment for year of birth, sex and BMI (OR=1.24, 95% CI 1.08-1.43, p=0.002 and OR=1.22, 95% CI 1.07-1.38, p=0.002, respectively). In the non-diabetic controls, the GG carriers of rs3817588 and rs780094 were nominally associated with a lower plasma triglyceride level compared to the AA carriers after adjustment for year of birth, sex and BMI (p for trend=0.00004 and 0.03, respectively). Furthermore, the association of rs3817588 with plasma triglyceride level was still significant after correcting for multiple testing. CONCLUSIONS: The rs3817588 A/G polymorphism of the GCKR gene was associated with type 2 diabetes and plasma triglyceride level in the Han Chinese population.

SUBMITTER: Ling Y

PROVIDER: S-EPMC3112072 | biostudies-literature | 2011

REPOSITORIES: biostudies-literature

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Associations of common polymorphisms in GCKR with type 2 diabetes and related traits in a Han Chinese population: a case-control study.

Ling Yan Y Li Xiaomu X Gu Qian Q Chen Hongyan H Lu Daru D Gao Xin X

BMC medical genetics 20110513

<h4>Background</h4>Several studies have shown that variants in the glucokinase regulatory protein gene (GCKR) were associated with type 2 diabetes and dyslipidemia. The purpose of this study was to examine whether tag single nucleotide polymorphisms (SNPs) in the GCKR region were associated with type 2 diabetes and related traits in a Han Chinese population and to identify the potential mechanisms underlying these associations.<h4>Methods</h4>We investigated the association of polymorphisms in t ...[more]

PMID: 21569451

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Project description:Gout is a common arthritic disease resulting from elevated serum uric acid (SUA) level. A large meta-analysis including 28,141 individuals identified nine single nucleotide polymorphisms (SNPs) associated with altered SUA level in a Caucasian population. However, raised SUA level alone is not sufficient for the development of gout arthritis and most of these SNPs have not been studied in a Han Chinese population. Here, we performed a case-control association analysis to investigate the relationship between these SUA correlated SNPs and gout arthritis in Han Chinese.A total of 622 ascertained gout p9atients and 917 healthy controls were genotyped. Genome-wide significant SNPs, rs12129861, rs780094, rs734553, rs742132, rs1183201, rs12356193, rs17300741 and rs505802 in the previous SUA study, were selected for our analysis.No deviation from the Hardy-Weinberg equilibrium was observed either in the case or control cohorts (corrected p?>?0.05). Three SNPs, rs780094 (located in GCKR, corrected p?=?1.78E(-4), OR?=?0.723), rs1183201 (located in SLC17A1, corrected p?=?1.39E(-7), OR?=?0.572) and rs505802 (located in SLC22A12, corrected p?=?0.007, OR?=?0.747), were significantly associated with gout on allelic level independent of potential cofounding traits. While the remaining SNPs were not replicated. We also found significant associations of uric acid concentrations with these three SNPs (rs780094 in GCKR, corrected p?=?3.94E(-5); rs1183201 in SLC17A1, corrected p?=?0.005; rs505802 in SLC22A12, corrected p?=?0.003) and of triglycerides with rs780094 (located in GCKR, corrected p?=?2.96E(-4)). Unfortunately, SNP-SNP interactions for these three significant SNPs were not detected (rs780094 vs rs1183201, p?=?0.402; rs780094 vs rs505802, p?=?0.434; rs1183201 vs rs505802, p?=?0.143).Three SUA correlated SNPs in Caucasian population, rs780094 in GCKR, rs1183201 in SLC17A1 and rs505802 in SLC22A12 were confirmed to be associated with gout arthritis and uric acid concentrations in Han Chinese males. Considering genetic differences among populations and complicated pathogenesis of gout arthritis, more validating tests in independent populations and relevant functional experiments are suggested in future.

Dataset Information

Associations of common polymorphisms in GCKR with type 2 diabetes and related traits in a Han Chinese population: a case-control study.

Publications

Associations of common polymorphisms in GCKR with type 2 diabetes and related traits in a Han Chinese population: a case-control study.

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