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

Diabetes. 2006 Dec;55(12):3620-4. doi: 10.2337/db06-0867.

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.

Publication types

  • Multicenter Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Substitution*
  • Apoptosis Regulatory Proteins
  • Arginine
  • Case-Control Studies
  • Cell Cycle Proteins / genetics*
  • Codon / genetics
  • Diabetes Mellitus, Type 2 / genetics*
  • Glutamine
  • Humans
  • Parents
  • Polymorphism, Genetic*
  • Polymorphism, Single Nucleotide
  • Repressor Proteins / genetics*
  • Siblings

Substances

  • Apoptosis Regulatory Proteins
  • Cell Cycle Proteins
  • Codon
  • KLF11 protein, human
  • Repressor Proteins
  • Glutamine
  • Arginine