Saif-Ali Riyadh, Ismail Ikram S, Al-Hamodi Zaid, Al-Mekhlafi Hesham M, Siang Lee C, Alabsi Aied M, Muniandy Sekaran
Department of Molecular Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur 50603, Malaysia; E-Mails:
Int J Mol Sci. 2011;12(9):5705-18. doi: 10.3390/ijms12095705. Epub 2011 Sep 5.
The aim of this study was to investigate the association of single nucleotide polymorphisms (SNPs) and haplotypes of potassium voltage-gated channel, KQT-like subfamily, member 1 (KCNQ1) with type 2 diabetes (T2D) in Malaysian Chinese subjects. The KCNQ1 SNPs rs2237892, rs2283228 and rs2237895 were genotyped in 300 T2D patients and 230 control subjects without diabetes and metabolic syndrome. Two logistic regression models of analysis were applied, the first adjusted for age and gender while the second adjusted for age, gender and body mass index. The additive genetic analysis showed that adjusting for body mass index (BMI) even strengthened association of rs2237892, rs2283228 and rs2237895 with T2D (OR = 2.0, P = 5.1 × 10(-5); OR = 1.9, P = 5.2 × 10(-5); OR = 1.9, P = 7.8 × 10(-5), respectively). The haplotype TCA containing the allele of rs2237892 (T), rs2283228 (C) and rs2237895 (A) was highly protective against T2D (Second model; OR = 0.17, P = 3.7 × 10(-11)). The KCNQ1 rs2237892 (TT), and the protective haplotype (TCA) were associated with higher beta-cell function (HOMA-B) in normal subjects (P = 0.0002; 0.014, respectively). This study found that KCNQ1 SNPs was associated with T2D susceptibility in Malaysian Chinese subjects. In addition, certain KCNQ1 haplotypes were strongly associated with T2D.
本研究旨在调查马来西亚华裔人群中钾离子电压门控通道KQT样亚家族成员1（KCNQ1）的单核苷酸多态性（SNP）和单倍型与2型糖尿病（T2D）的关联。对300例T2D患者和230例无糖尿病及代谢综合征的对照受试者进行KCNQ1 SNPs rs2237892、rs2283228和rs2237895基因分型。应用两种逻辑回归分析模型，第一种模型对年龄和性别进行校正，第二种模型对年龄、性别和体重指数进行校正。加性遗传分析表明，校正体重指数（BMI）后，rs2237892、rs2283228和rs2237895与T2D的关联增强（OR分别为2.0，P = 5.1×10⁻⁵；OR = 1.9，P = 5.2×10⁻⁵；OR = 1.9，P = 7.8×10⁻⁵）。包含rs2237892（T）、rs2283228（C）和rs2237895（A）等位基因的单倍型TCA对T2D具有高度保护作用（第二种模型；OR = 0.17，P = 3.7×10⁻¹¹）。KCNQ1 rs2237892（TT）以及保护性单倍型（TCA）与正常受试者较高的β细胞功能（HOMA - B）相关（P分别为0.0002；0.014）。本研究发现，KCNQ1 SNPs与马来西亚华裔人群的T2D易感性相关。此外，某些KCNQ1单倍型与T2D密切相关。
