Transcription factor 7-like 2 (TCF7L2) is associated with gestational diabetes mellitus and interacts with adiposity to alter insulin secretion in Mexican Americans
Transcription factor 7-like 2 (TCF7L2) is associated with gestational diabetes mellitus and interacts with adiposity to alter insulin secretion in Mexican Americans
复制标题
DOI：
10.2337/db06-1682
复制
发表时间：
2007-05-01
期刊：
影响因子：
7.7
通讯作者：
Buchanan, Thomas A.
中科院分区：
文献类型：
--
作者：
Watanabe, Richard M.;Allayee, Hooman;Buchanan, Thomas A.
转录因子7样2（TCF 7 L2）基因变异与2型糖尿病及糖尿病相关数量性状相关。我们在132个有妊娠期糖尿病（GDM）先证者的墨西哥裔美国人家庭中检测了标记物DG 10 S478周围0.1Mb区域的变异与糖尿病相关的数量性状的关系。研究设计和方法研究参与者通过口服葡萄糖耐量试验（OGTT）和静脉内葡萄糖耐量试验以及双能X-射线光片进行表型分析。用X线吸收仪扫描身体脂肪的百分比。在42个标签单核苷酸多态性（SNP）基因分型，15个被确定。然而，rs 12255372显示与30' Delta胰岛素（OGTT 30' min空腹胰岛素）在与体脂百分比的相互作用中相关（Bonferroni校正的P = 0.027）。肥胖对增加30'D胰岛素的影响在携带T等位基因的受试者中更大。这种相互作用与静脉注射葡萄糖的急性胰岛素反应无关。rs 12255372还显示与基于30'D胰岛素的胰岛素抵抗的β细胞补偿在与体脂百分比的相互作用中相关（Bonferroni校正的P = 0.014）。rs 12255372在我们的病例对照样本中也与GDM相关（优势比[OR] 2.49 [95%CI 1.17-5.31]; P = 0.018）。结论-我们得出结论TCF 7 L2的变异与GDM相关，并与肥胖相互作用，改变墨西哥裔美国人的胰岛素分泌。我们的观察部分解释了在以前的相关研究中观察到的OR增加，分析仅限于瘦的受试者和数量性状关联结果的变异性。
OBJECTIVE-Variation in transcription factor 7-like 2 (TCF7L2) gene has been shown to be associated with type 2 diabetes and diabetes-related quantitative traits. We examined variation in a 0.1-Mb region surrounding marker DG10S478 for association with diabetes-related quantitative traits in 132 Mexican-American families of a proband with previous gestational diabetes mellitus (GDM).RESEARCH DESIGN AND METHODS-Study participants were phenotyped by an oral glucose tolerance test (OGTT) and an intravenous glucose tolerance test and by a dual-energy X-ray absorptiometry scan for percentage of body fat. Of the 42 tag single nucleotide polymorphisms (SNPs) genotyped, 15 were identified.RESULTS-On univariate analysis, none of the SNPs showed association with diabetes-related quantitative traits. However, rs12255372 showed association with 30' Delta insulin (OGTT 30' min fasting insulin) in an interaction with percentage of body fat (Bonferroni-corrected P = 0.027). The effect of adiposity to increase 30' Dinsulin was greater in subjects with the T allele. This interaction was not associated with acute insulin response to intravenous glucose. rs12255372 also showed an association with [beta-cell compensation for insulin resistance based on 30' Dinsulin in an interaction with percentage of body fat (Bonferroni-corrected P = 0.014). rs12255372 was also associated with GDM (odds ratio [OR] 2.49 [95% CI 1.17-5.31]; P = 0.018) in our case-control sample.CONCLUSIONS-We conclude that variation in TCF7L2 is associated with GDM and interacts with adiposity to alter insulin secretion in Mexican Americans. Our observations partly explain the increased ORs observed in previous associated studies when analyses were restricted to lean subjects and the variability in quantitative trait association results.