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. Sale12345,
- Shelly G. Smith1,
- Josyf C. Mychaleckyj367,
- Keith L. Keene1,
- Carl D. Langefeld7,
- Tennille S. Leak1,
- Pamela J. Hicks18,
- Donald W. Bowden128,
- Stephen S. Rich346 and
- Barry I. Freedman2
- 1Center for Human Genomics, Wake Forest University School of Medicine, Winston-Salem, North Carolina
- 2Department of Internal Medicine, Wake Forest University School of Medicine, Winston-Salem, North Carolina
- 3Center for Public Health Genomics, University of Virginia, Charlottesville, Virginia
- 4Department of Medicine, University of Virginia, Charlottesville, Virginia
- 5Department of Biochemistry and Molecular Genetics, University of Virginia, Charlottesville, Virginia
- 6Department of Public Health Sciences, University of Virginia, Charlottesville, Virginia
- 7Division of Public Health Sciences, Wake Forest University School of Medicine, Winston-Salem, North Carolina
- 8Department 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 Pa = 3.77 × 10−6) and rs7901695 (P = 0.001, OR 1.30; Pa = 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 < Pa < 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 < Pa < 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
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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 therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
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- Accepted June 22, 2007.
- Received January 5, 2007.
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