Association of transcription factor 7-like 2 (TCF7L2) variants with type 2 diabetes in a Finnish sample
Association of transcription factor 7-like 2 (TCF7L2) variants with type 2 diabetes in a Finnish sample
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DOI：
10.2337/db06-0341
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发表时间：
2006-09-01
期刊：
影响因子：
7.7
通讯作者：
Boehnke, Michael
中科院分区：
文献类型：
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作者：
Scott, Laura J.;Bonnycastle, Lori L.;Boehnke, Michael
转录因子7样2（TCF 7 L2）是Wnt信号通路的一部分。最近报道，染色体10 q上TCF 7 L2内的遗传变异与冰岛人、丹麦人和美国人的2型糖尿病相关。样品我们先前在芬兰-美国NIDDM遗传学研究调查中观察到染色体10 q上的比值分数为0.61的适度对数，类似于TCF 7 L2的1 Mb。我们在芬兰的1,151例2型糖尿病患者和953例对照受试者样本中检测了5种相关的TCF 7 L2单核苷酸多态性（SNP）变异。我们证实了所有五个SNP与相同风险等位基因的关联（P值< 0.05）。我们最强的结果是rs 1255372（比值比[OR] 1.36 [95%CI 1.15-1.61]，P = 0.00026）和rs7903146（1.33 [1.14-1.56]，P = 0.00042）。基于CEU HapMap数据，我们选择并测试了12个额外的SNP来标记与rs 1255372连锁不平衡的SNP。这些SNPs中没有一个显示出比rs 12255372或rs7903146更强的关联证据（OR = 0.0054）。我们的研究结果加强了TCF 7 L2中一种或多种变异与2型糖尿病风险增加相关的证据。
Transcription factor 7-like 2 (TCF7L2) is part of the Wnt signaling pathway. Genetic variants within TCF7L2 on chromosome 10q were recently reported to be associated with type 2 diabetes in Icelandic, Danish, and American (U.S.) samples. We previously observed a modest logarithm of odds score of 0.61 on chromosome 10q, similar to 1 Mb from TCF7L2, in the Finland-United States Investigation of NIDDM Genetics study. We tested the five associated TCF7L2 single nucleotide polymorphism (SNP) variants in a Finnish sample of 1,151 type 2 diabetic patients and 953 control subjects. We confirmed the association with the same risk allele (P value < 0.05) for all five SNPs. Our strongest results were for rs1255372 (odds ratio [OR] 1.36 [95% CI 1.15-1.61], P = 0.00026) and rs7903146 (1.33 [1.14-1.56], P = 0.00042). Based on the CEU HapMap data, we selected and tested 12 additional SNPs to tag SNPs in linkage disequilibrium with rs1255372. None of these SNPs showed stronger evidence of association than rs12255372 or rs7903146 (OR = 0.0054). Our results strengthen the evidence that one or more variants in TCF7L2 are associated with increased risk of type 2 diabetes.