The TCF7L2 Diabetes Risk Variant is Associated with HbA1C Levels: a Genome-Wide Association Meta-Analysis

被引：28

作者：

Franklin, Christopher S. ^{[1
]}

Aulchenko, Yurii S. ^{[2
]}

Huffman, Jennifer E. ^{[3
]}

Vitart, Veronique ^{[3
]}

Hayward, Caroline ^{[3
]}

Polasek, Ozren ^{[4
,5
]}

Knott, Sara ^{[6
]}

Zgaga, Lina ^{[1
,5
]}

Zemunik, Tatijana ^{[7
]}

Rudan, Igor ^{[1
,4
,7
]}

Campbell, Harry ^{[1
]}

Wright, Alan F. ^{[3
]}

Wild, Sarah H. ^{[1
]}

Wilson, James F. ^{[1
]}

机构：

[1] Univ Edinburgh, Ctr Populat Hlth Sci, Edinburgh EH8 9AG, Midlothian, Scotland

[2] Erasmus MC, Genet Epidemiol Unit, Dept Epidemiol & Biostat, Rotterdam, Netherlands

[3] Western Gen Hosp, Inst Genet & Mol Med, MRC Human Genet Unit, Edinburgh EH4 2XU, Midlothian, Scotland

[4] Gen Info Ltd, Zagreb 10000, Croatia

[5] Univ Zagreb, Sch Med, Andrija Stampar Sch Publ Hlth, Zagreb 41001, Croatia

[6] Univ Edinburgh, Inst Evolutionary Biol, Edinburgh EH9 3JT, Midlothian, Scotland

[7] Univ Split, Sch Med, Croatian Ctr Global Hlth, Split, Croatia

来源：

ANNALS OF HUMAN GENETICS | 2010年 / 74卷

基金：

英国医学研究理事会;

关键词：

HbA(1C); association; TCF7L2; isolate population; diabetes; meta-analysis; GLUCOSE-LEVELS; GENE; LOCI; SUSCEPTIBILITY; CROATIA; MTNR1B; ISLAND;

D O I：

10.1111/j.1469-1809.2010.00607.x

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

P>Genome-wide association (GWA) studies have identified around 20 common genetic variants influencing the risk of type 2 diabetes (T2D). Likewise, a number of variants have been associated with diabetes-related quantitative glycaemic traits, but to date the overlap between these genes and variants has been low. The majority of genetic studies have focused on fasting plasma glucose levels; however, this measure is highly variable. We have conducted a GWA meta-analysis of glycated haemoglobin (HbA(1C)) levels within three healthy nondiabetic populations. This phenotype provides an estimate of mean glucose levels over 2-3 months and is a more stable predictor of future diabetes risk. Participants were from three isolated populations: the Orkney Isles in the north of Scotland, the Dalmatian islands of Vis, and Korcula in Croatia (total of 1782 nondiabetic subjects). Association was tested in each population and results combined by meta-analysis. The strongest association was with the TCF7L2 gene (rs7903146, P = 1.48 x 10-7). This is also the strongest common genetic risk factor for T2D but it has not been identified in previous genome-wide studies of glycated haemoglobin.

引用

页码：471 / 478

页数：8

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