Zhang Cuilin, Qi Lu, Hunter David J, Meigs James B, Manson JoAnn E, van Dam Rob M, Hu Frank B
Department of Nutrition, Harvard School of Public Health, Boston, MA 02115, USA.
Diabetes. 2006 Sep;55(9):2645-8. doi: 10.2337/db06-0643.
Emerging evidence indicates that variation in the transcription factor 7-like 2 (TCF7L2) gene may play a role in the pathogenesis of type 2 diabetes. In a prospective, nested, case-control study (n = 3,520) within the Nurses' Health Study (687 type 2 diabetic case and 1,051 control subjects) and the Health Professionals Follow-up Study (886 case and 896 control subjects), we examined the association of a common variant of the TCF7L2 gene (rs12255372 [T/G]) with type 2 diabetes risk among Caucasians. Frequencies of the T-allele were significantly higher among case than control subjects; each copy of the T-allele was associated with a 1.32-fold (P = 0.0002) and 1.53-fold (P < 0.0001) increased type 2 diabetes risk in women and men, respectively. The odds ratios (95% CI) associated with homozygous carriers of the T-allele were 1.86 (1.30-2.67) and 2.15 (1.48-3.13) in women and men, respectively. Population-attributable risks for diabetes associated with the T-allele were 14.8 and 22.3% for women and men, respectively. In a meta-analysis of 3,347 case and 3,947 control subjects, each copy of the T-allele was associated with a 1.48-fold increased risk (P < 10(-16)). Our findings confirm that the TCF7L2 gene represents an important locus for predicting inherited susceptibility to type 2 diabetes.
新出现的证据表明，转录因子7样2（TCF7L2）基因的变异可能在2型糖尿病的发病机制中起作用。在护士健康研究（687例2型糖尿病病例和1051例对照受试者）和卫生专业人员随访研究（886例病例和896例对照受试者）中的一项前瞻性、巢式病例对照研究（n = 3520）中，我们研究了TCF7L2基因的一个常见变异（rs12255372 [T/G]）与白种人中2型糖尿病风险的关联。病例组中T等位基因的频率显著高于对照组；在女性和男性中，T等位基因的每一个拷贝分别与2型糖尿病风险增加1.32倍（P = 0.0002）和1.53倍（P < 0.0001）相关。T等位基因纯合携带者的优势比（95% CI）在女性和男性中分别为1.86（1.30 - 2.67）和2.15（1.48 - 3.13）。与T等位基因相关的糖尿病人群归因风险在女性和男性中分别为14.8%和22.3%。在对3347例病例和3947例对照受试者的荟萃分析中，T等位基因的每一个拷贝与风险增加1.48倍相关（P < 10^(-16)）。我们的研究结果证实，TCF7L2基因是预测2型糖尿病遗传易感性的一个重要位点。
