Transcription Factor 7-Like 2 (TCF7L2) Polymorphism and Context-Specific Risk of Type 2 Diabetes in African American and Caucasian Adults: The Atherosclerosis Risk in Communities (ARIC) Study.

  1. Yu Yan, MD, MPH1,
  2. Kari E. North, PhD (kari_north{at}unc.edu)1,2,
  3. Christie M. Ballantyne, MD (kari_north{at}unc.edu)3,
  4. Frederick L. Brancati, MD,MHS4,5,
  5. Lloyd E. Chambless, PhD6,
  6. Nora Franceschini, MD, MPH1,
  7. Gerardo Heiss, MD, PhD1,
  8. Anna Kottgen, MD, MPH4,
  9. James S. Pankow, PhD7,
  10. Elizabeth Selvin, PhD, MPH4,
  11. Suzanne L. West, MPH, PhD1 and
  12. Eric Boerwinkle, PhD8
  1. 1Department of Epidemiology, University of North Carolina, Chapel Hill NC
  2. 2Carolina Center for Genome Sciences, University of North Carolina, Chapel Hill NC
  3. 3Department of Medicine, Atherosclerosis and Vascular Medicine, Baylor College of Medicine, Houston TX
  4. 4Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore MD
  5. 5Department of Medicine, Johns Hopkins University, Baltimore MD
  6. 6Department of Biostatistics, University of North Carolina, Chapel Hill NC
  7. 7Division of Epidemiology and Community Health, University of Minnesota, Minneapolis MN
  8. 8Human Genetics Center, University of Texas-Houston Health Science Center, Houston TX

    Abstract

    OBJECTIVE: Although variants in the transcription factor 7-like 2 (TCF7L2) gene are consistently associated with type 2 diabetes mellitus (T2DM), large population-based studies of African Americans are lacking. Moreover, few studies have investigated the effects of TCF7L2 on T2DM in the context of metabolic risk factors of T2DM.

    RESEARCH DESIGN AND METHODS: We investigated the association between the TCF7L2 rs7903146 polymorphism and T2DM in 2,727 African American and 9,302 Caucasian participants without diabetes inducted into the Atherosclerosis Risk in Communities Study in 1987-1989 and followed for 9 years.

    RESULTS: A total of 485 and 923 cases of T2DM were identified in African-Americans and Caucasians, respectively. Compared to homozygous CC individuals, heterozygous CT and homozygous TT individuals had higher cumulative incidence (95%CI) of T2DM over 9 years of follow-up, 11.3% (CI=10.2, 12.4%) vs. 21.1% (20.8, 21.4%) and 27.9% (19.3, 36.5%) in African-Americans, 9.7% (8.8, 10.6%) vs. 11.3% (10.2, 12.4%) and 13.6% (11.1, 16.1%) in Caucasians. Individuals with the risk allele had the highest hazards of diabetes if they were obese and had low HDL, followed by individuals with any one, and none of the traits.

    CONCLUSIONS: Our study provides the first significant evidence of association between the TCF7L2 rs7903146 polymorphism and T2DM risk in a large African American population, and also demonstrates that the diabetes risk conveyed by the rs7903146 risk allele is substantially increased in the context of some metabolic risk factors for T2DM. Our study findings need to be replicated in other large, population-based studies.

    Footnotes

      • Received April 26, 2008.
      • Accepted October 8, 2008.

    This Article

    1. Published online before print October 17, 2008, doi: 10.2337/db08-0569
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