Variants of the Transcription Factor 7-Like 2 (TCF7L2) Gene Are Associated With Type 2 Diabetes in an African-American Population
Enriched for Nephropathy
Michèle M. Sale 1 2 3 4 5 ,
Shelly G. Smith 1 ,
Josyf C. Mychaleckyj 3 6 7 ,
Keith L. Keene 1 ,
Carl D. Langefeld 7 ,
Tennille S. Leak 1 ,
Pamela J. Hicks 1 8 ,
Donald W. Bowden 1 2 8 ,
Stephen S. Rich 3 4 6 and
Barry I. Freedman 2
1 Center for Human Genomics, Wake Forest University School of Medicine, Winston-Salem, North Carolina
2 Department of Internal Medicine, Wake Forest University School of Medicine, Winston-Salem, North Carolina
3 Center for Public Health Genomics, University of Virginia, Charlottesville, Virginia
4 Department of Medicine, University of Virginia, Charlottesville, Virginia
5 Department of Biochemistry and Molecular Genetics, University of Virginia, Charlottesville, Virginia
6 Department of Public Health Sciences, University of Virginia, Charlottesville, Virginia
7 Division of Public Health Sciences, Wake Forest University School of Medicine, Winston-Salem, North Carolina
8 Department of Biochemistry, Wake Forest University School of Medicine, Winston-Salem, North Carolina
Address correspondence and reprint requests to Michèle M. Sale, PhD, Center for Public Health Genomics, University of Virginia,
P.O. Box 800717, Charlottesville, VA 22908. E-mail: msale{at}virginia.edu
Abstract
OBJECTIVE— Recently, variants in the TCF7L2 gene have been reported to be associated with type 2 diabetes across multiple Europid populations,
but only one small sample of African-American type 2 diabetic patients has been examined. Our objective was to investigate
the importance of TCF7L2 in a larger African-American case-control population.
RESEARCH DESIGN AND METHODS— We investigated single nucleotide polymorphisms (SNPs) in six known type 2 diabetes genes in 577 African-American case subjects
with type 2 diabetes enriched for nephropathy and 596 African-American control subjects. Additionally, we genotyped 70 ancestry-informative
markers (AIMs) to apply adjustments for differences in ancestral proportions.
RESULTS— The most significant associations were observed with TCF7L2 intron 3 SNPs rs7903146 (additive P = 4.10 × 10 −6 , odds ratio [OR] 1.51; admixture-adjusted P a = 3.77 × 10 −6 ) and rs7901695 ( P = 0.001, OR 1.30; P a = 0.003). The 2-SNP haplotype containing these SNPs was also associated with type 2 diabetes ( P = 3 × 10 −5 ). Modest associations were also seen with TCF7L2 intron 4 SNPs rs7895340, rs11196205, and rs12255372 (0.01 < P < 0.05; 0.03 < P a < 0.08), as well as with ATP-sensitive inwardly rectifying potassium channel subunit Kir6.2 (KCNJ11) and hepatocyte nuclear
factor 4-α (HNF4A) SNPs (0.01 < P < 0.05; 0.01 < P a < 0.41). No significant associations were detected with genotyped calpain 10 (CAPN10), peroxisome proliferator–activated
receptor γ (PPARG), and transcription factor 1 (TCF1) SNPs.
CONCLUSIONS— This study indicates that variants in the TCF7L2 gene significantly contribute to diabetes susceptibility in African-American
populations.
AIM, ancestry-informative marker
HWE, Hardy-Weinberg equilibrium
SNP, single nucleotide polymorphism
Footnotes
Published ahead of print at http://diabetes.diabetesjournals.org on 29 June 2007. DOI: 10.2337/db07-0012.
Additional information for this article can be found in an online appendix at http://dx.doi.org/10.2337/db07-0012 .
The costs of publication of this article were defrayed in part by the payment of page charges. This article must the...

Variants of the Transcription Factor 7-Like 2 (TCF7L2) Gene Are Associated With Type 2 Diabetes in an African-American Population Enriched for Nephropathy

10.2337/db07-0012