Department of Endocrinology and Metabolism, Zhongshan Hospital, Fudan University, Shanghai 200032, China.
BMC Med Genet. 2011 May 13;12:66. doi: 10.1186/1471-2350-12-66.
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.
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.
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.
The rs3817588 A/G polymorphism of the GCKR gene was associated with type 2 diabetes and plasma triglyceride level in the Han Chinese population.
多项研究表明，葡萄糖激酶调节蛋白基因（GCKR）的变异与 2 型糖尿病和血脂异常有关。本研究旨在探讨汉族人群中 GCKR 区域的标签单核苷酸多态性（SNP）是否与 2 型糖尿病及相关特征相关，并确定这些关联的潜在机制。
采用病例对照研究设计（1118 例病例和 1161 例对照），研究 GCKR 基因多态性与 2 型糖尿病的关系。研究了 GCKR 基因及其侧翼区域内的 4 个标签 SNP（rs8179206、rs2293572、rs3817588 和 rs780094），这些 SNP 之间的成对 r2>0.8，且次要等位基因频率>0.05，并构建了单倍型。采用基质辅助激光解吸/电离飞行时间质谱联用技术，利用 MassARRAY 平台进行基因分型。
校正出生年份、性别和 BMI 后，GCKR rs3817588 和 rs780094 的 G 等位基因与 2 型糖尿病的发病风险增加相关（OR=1.24，95%CI 1.08-1.43，p=0.002 和 OR=1.22，95%CI 1.07-1.38，p=0.002）。在非糖尿病对照组中，校正出生年份、性别和 BMI 后，rs3817588 和 rs780094 的 GG 携带者的血浆甘油三酯水平与 AA 携带者相比，具有名义上的相关性（p 趋势=0.00004 和 0.03）。此外，在校正多重检验后，rs3817588 与血浆甘油三酯水平的关联仍然显著。
汉族人群中，GCKR 基因的 rs3817588 A/G 多态性与 2 型糖尿病和血浆甘油三酯水平相关。
