HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Online-Only Appendix All Versions of this Article: db07-0012v1 56/10/2638    most recent Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Sale, M. M. Articles by Freedman, B. I. Search for Related Content PubMed PubMed Citation Articles by Sale, M. M. Articles by Freedman, B. I. Social Bookmarking                What's this?

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

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

Abbreviations: AIM, ancestry-informative marker; HWE, Hardy-Weinberg equilibrium; SNP, single nucleotide polymorphism

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 x 10^–6, odds ratio [OR] 1.51; admixture-adjusted P_a = 3.77 x 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 x 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- (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 (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.

CiteULike    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				K. L. Keene, J. C. Mychaleckyj, S. G. Smith, T. S. Leak, P. S. Perlegas, C. D. Langefeld, B. I. Freedman, S. S. Rich, D. W. Bowden, and M. M. Sale Association of the Distal Region of the Ectonucleotide Pyrophosphatase/Phosphodiesterase 1 Gene With Type 2 Diabetes in an African-American Population Enriched for Nephropathy Diabetes, April 1, 2008; 57(4): 1057 - 1062. [Abstract] [Full Text] [PDF]

				M. O. Goodarzi and J. I. Rotter Testing the Gene or Testing a Variant?: The Case of TCF7L2 Diabetes, October 1, 2007; 56(10): 2417 - 2419. [Full Text] [PDF]