Variant of transcription factor 7-like 2 (TCF7L2) gene confers risk of type 2 diabetes
Variant of transcription factor 7-like 2 (TCF7L2) gene confers risk of type 2 diabetes
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DOI：
10.1038/ng1732
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发表时间：
2006-03-01
期刊：
影响因子：
30.8
通讯作者：
Stefansson, K
中科院分区：
文献类型：
--
作者：
Grant, SFA;Thorleifsson, G;Stefansson, K
我们先前已经报道了2型糖尿病与10q染色体（1）的暗示性联系。我们在10Q的10.5-MB间隔中基因分型在具有2型糖尿病和对照的冰岛个体中的228个微卫星标记。在转录因子7样基因（TCF7L2;以前的TCF4）的内含子3中的微卫星DG10S478与2型糖尿病有关（p = 2.1 x 10（-9））。这是在丹麦队列（p = 4.8 x 10（-3））和美国队列中复制的（p = 3.3 x 10（-9））。与非携带者相比，高危等位基因的杂合和纯合载体（分别为38％和7％）的相对风险为1.45和2.41。这对应于21％的人口风险。 TCF7L2基因产物是一个含有血糖稳态的高迁移率组盒子转录因子。人们认为它可以通过Wnt信号通路（2）调节肠内分泌细胞中的proglucagon基因表达作用。
We have previously reported suggestive linkage of type 2 diabetes mellitus to chromosome 10q(1). We genotyped 228 microsatellite markers in Icelandic individuals with type 2 diabetes and controls throughout a 10.5-Mb interval on 10q. A microsatellite, DG10S478, within intron 3 of the transcription factor 7-like 2 gene (TCF7L2; formerly TCF4) was associated with type 2 diabetes (P = 2.1 X 10(-9)). This was replicated in a Danish cohort (P = 4.8 X 10(-3)) and in a US cohort (P = 3.3 X 10(-9)). Compared with non-carriers, heterozygous and homozygous carriers of the at-risk alleles (38% and 7% of the population, respectively) have relative risks of 1.45 and 2.41. This corresponds to a population attributable risk of 21%. The TCF7L2 gene product is a high mobility group box-containing transcription factor previously implicated in blood glucose homeostasis. It is thought to act through regulation of proglucagon gene expression in enteroendocrine cells via the Wnt signaling pathway(2).