Role of a Proline Insertion in the Insulin Promoter Factor 1 (IPF1) Gene in African Americans With Type 2 Diabetes

  1. Steven C. Elbein12,
  2. Xiaoqin Wang12,
  3. Mohammad A. Karim3,
  4. Barry I. Freedman4,
  5. Donald W. Bowden5,
  6. Alan R. Shuldiner67,
  7. Frederick L. Brancati89 and
  8. Wen Hong Linda Kao9
  1. 1Endocrinology Section, Central Arkansas Veterans Healthcare System, Little Rock, Arkansas
  2. 2Division of Endocrinology, Department of Medicine, College of Medicine, University of Arkansas for Medical Sciences, Little Rock, Arkansas
  3. 3Department of Pediatrics, College of Medicine, University of Arkansas for Medical Sciences, Little Rock, Arkansas
  4. 4Department of Medicine, Wake Forest University School of Medicine, Winston-Salem, North Carolina
  5. 5Center for Human Genomics, Wake Forest University School of Medicine, Winston-Salem, North Carolina
  6. 6Division of Endocrinology, Department of Medicine, University of Maryland School of Medicine, Baltimore, Maryland
  7. 7Geriatric Research and Education Clinical Center, Baltimore Veterans Administration Medical Center, Baltimore, Maryland
  8. 8Department of Medicine, Johns Hopkins School of Medicine, Baltimore, Maryland
  9. 9Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland
  1. Address correspondence and reprint requests to Steven C. Elbein, MD, Professor of Medicine, Division of Endocrinology 111J-1/LR, John L. McClellan Veterans Hospital, 4300 West 7th St., Little Rock, AR 72205-5446. E-mail: elbeinstevenc{at}uams.edu

Abstract

African Americans have twice the prevalence of type 2 diabetes as Caucasians and much greater genetic diversity. We identified an inframe insertion of a proline in the insulin promoter factor 1 (IPF1) gene (InsCCG243), which was relatively common (minor allele frequency ∼0.08) in African Americans and showed a trend to association with type 2 diabetes in preliminary studies. An earlier French study identified InsCCG243 as a cause of autosomal dominant diabetes. To determine the role of this variant in African Americans, we examined an additional population from North Carolina (n = 368) and a subset of African-American participants from the Atherosclerosis Risk in Communities (ARIC) study (n = 1,741). We also looked for segregation in 66 African-American families and for a role in insulin secretion in 112 nondiabetic subjects. InsCCG243 did not increase the risk of type 2 diabetes (P = 0.16 in North Carolina; P = 0.97 in the ARIC study) and did not segregate with type 2 diabetes in families. However, we found suggestive evidence for reduced insulin response to glucose (P = 0.05). Neither indirect measures of β-cell mass nor β-cell compensation were altered (P > 0.1). InsCCG243 does not act in a dominant, highly penetrant fashion in African Americans and is not a significant risk factor for type 2 diabetes in this population.

Footnotes

  • Additional information for this article can be found in an online appendix at http://diabetes.diabetesjournals.org.

  • 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.

    • Accepted June 27, 2006.
    • Received April 3, 2006.
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  1. doi: 10.2337/db06-0434 Diabetes October 2006 vol. 55 no. 10 2909-2914
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