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
    Center for Human Genomics, Wake Forest University School of Medicine, Winston-Salem, North Carolina
  • Shelly G. Smith
    Center for Human Genomics, Wake Forest University School of Medicine, Winston-Salem, North Carolina
  • Josyf C. Mychaleckyj
    Center for Public Health Genomics, University of Virginia, Charlottesville, Virginia
  • Keith L. Keene
    Center for Human Genomics, Wake Forest University School of Medicine, Winston-Salem, North Carolina
  • Carl D. Langefeld
    Division of Public Health Sciences, Wake Forest University School of Medicine, Winston-Salem, North Carolina
  • Tennille S. Leak
    Center for Human Genomics, Wake Forest University School of Medicine, Winston-Salem, North Carolina
  • Pamela J. Hicks
    Center for Human Genomics, Wake Forest University School of Medicine, Winston-Salem, North Carolina
  • Donald W. Bowden
    Center for Human Genomics, Wake Forest University School of Medicine, Winston-Salem, North Carolina
  • Stephen S. Rich
    Center for Public Health Genomics, University of Virginia, Charlottesville, Virginia
  • Barry I. Freedman
    Department of Internal Medicine, Wake Forest University School of Medicine, Winston-Salem, North Carolina

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Description

<jats:p>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.</jats:p> <jats:p>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.</jats:p> <jats:p>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 &lt; P &lt; 0.05; 0.03 &lt; Pa &lt; 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 &lt; P &lt; 0.05; 0.01 &lt; Pa &lt; 0.41). No significant associations were detected with genotyped calpain 10 (CAPN10), peroxisome proliferator–activated receptor γ (PPARG), and transcription factor 1 (TCF1) SNPs.</jats:p> <jats:p>CONCLUSIONS—This study indicates that variants in the TCF7L2 gene significantly contribute to diabetes susceptibility in African-American populations.</jats:p>

Journal

  • Diabetes

    Diabetes 56 (10), 2638-2642, 2007-10-01

    American Diabetes Association

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