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Leif Groop

Leif Groop

Principal investigator

Leif Groop

The Kruppel-like factor 11 (KLF11) Q62R polymorphism is not associated with type 2 diabetes in 8,676 people

Author

  • Jose C. Florez
  • Richa Saxena
  • Wendy Winckler
  • Noel P. Burtt
  • Peter Almgren
  • Kristina Bengtsson Boström
  • Tiinamaija Tuomi
  • Daniel Gaudet
  • Kristin G. Ardlie
  • Mark J. Daly
  • David Altshuler
  • Joel N. Hirschhorn
  • Leif Groop

Summary, in English

Kruppel-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% Cl 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.

Department/s

  • Genomics, Diabetes and Endocrinology

Publishing year

2006

Language

English

Pages

3620-3624

Publication/Series

Diabetes

Volume

55

Issue

12

Document type

Journal article

Publisher

American Diabetes Association Inc.

Topic

  • Endocrinology and Diabetes

Status

Published

Research group

  • Genomics, Diabetes and Endocrinology

ISBN/ISSN/Other

  • ISSN: 1939-327X