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.

Figure 1

Acute insulin response (AIR) and acute C-peptide response (ACPR) stratified according to GCKR rs780094 or rs3817588 genotypes by quartile of diabetic duration. * p < 0.05 compared with homozygote of major allele (AA) ** p < 0.01 compared with homozygote of major allele (AA) # p for trend < 0.05 All p values were not significant after Bonferroni correction (p < 0.0016 (0.05/32) was used as Bonferroni corrected statistically significant level in association analysis between the individual SNP and AIR or ACPR) The figures below the genotypes indicate the number of diabetic cases for each genotype group.