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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 r 2  > 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.

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