The Krüppel-Like Factor 11 (KLF11) Q62R Polymorphism Is Not Associated With Type 2 Diabetes in 8,676 People

  1. Jose C. Florez1234,
  2. Richa Saxena14,
  3. Wendy Winckler5,
  4. Noël P. Burtt4,
  5. Peter Almgren6,
  6. Kristina Bengtsson Boström7,
  7. Tiinamaija Tuomi89,
  8. Daniel Gaudet10,
  9. Kristin G. Ardlie11,
  10. Mark J. Daly24,
  11. David Altshuler123412,
  12. Joel N. Hirschhorn41213 and
  13. Leif Groop68
  1. 1Department of Molecular Biology and Center for Human Genetic Research, Massachusetts General Hospital, Boston, Massachusetts
  2. 2Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts
  3. 3Department of Medicine, Harvard Medical School, Boston, Massachusetts
  4. 4Medical and Population Genetics Program, Broad Institute of Harvard and MIT, Cambridge, Massachusetts
  5. 5Cancer Biology Program, Broad Institute of Harvard and MIT, Cambridge, Massachusetts
  6. 6Department of Endocrinology, University Hospital MAS, Lund University, Malmö, Sweden
  7. 7Department of Clinical Science, University Hospital MAS, Lund University, Malmö, Sweden
  8. 8Department of Medicine, Helsinki University Central Hospital and Research Program for Molecular Medicine, University of Helsinki, Helsinki, Finland
  9. 9Folkhälsan Genetic Institute, Folkhälsan Research Center, Helsinki, Finland
  10. 10University of Montreal Community Genomic Center, Chicoutimi Hospital, Chicoutimi, Quebec, Canada
  11. 11Genomics Collaborative Division, SeraCare LifeSciences, Cambridge, Massachusetts
  12. 12Department of Genetics, Harvard Medical School, Boston, Massachusetts
  13. 13Divisions of Genetics and Endocrinology, Children’s Hospital, Boston, Massachusetts
  1. Address correspondence and reprint requests to Jose C. Florez, Simches Research Building, CPZN 6820, Diabetes Unit/Center for Human Genetic Research, Massachusetts General Hospital, Boston, MA 02114. E-mail: jcflorez{at}partners.org

Abstract

Krüppel-like factor 11 is a pancreatic transcription factor whose activity induces the insulin gene. A common glutamine-to-arginine change at codon 62 (Q62R) in its gene KLF11 has been recently associated with type 2 diabetes in two independent samples. Q62R and two other rare missense variants (A347S and T220M) were also shown to affect the function of KLF11 in vitro, and insulin levels were lower in carriers of the minor allele at Q62R. We therefore examined their impact on common type 2 diabetes in several family-based and case-control samples of northern-European ancestry, totaling 8,676 individuals. We did not detect the rare A347S and T220M variants in our samples. With respect to Q62R, despite >99% power to detect an association of the previously published magnitude, Q62R was not associated with type 2 diabetes (pooled odds ratio 0.97 [95% CI 0.88–1.08], P = 0.63). In a subset of normoglycemic individuals, we did not observe significant differences in various insulin traits according to genotype at KLF11 Q62R. We conclude that the KLF11 A347S and T220M mutations do not contribute to increased risk of diabetes in European-derived populations and that the Q62R polymorphism has, at best, a minor effect on diabetes risk.

Footnotes

  • J.N.H. and L.G. contributed equally to this work.

    K.G.A. is currently affiliated with the Biological Samples Platform, Broad Institute of Harvard and Massachusetts Institute of Technology.

    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 August 21, 2006.
    • Received June 26, 2006.
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