Evaluation of the association of IGF2BP2 variants with type 2 diabetes in French Caucasians

Diabetes. 2008 Jul;57(7):1992-6. doi: 10.2337/db07-1789. Epub 2008 Apr 22.

Abstract

Objective: We performed a comprehensive genetic association study of common variation spanning the IGF2BP2 locus in order to replicate the association of the "confirmed" type 2 diabetes susceptibility variants rs4402960 and rs1470579 in the French Caucasian population and to further characterize the susceptibility variants at this novel locus.

Research design and methods: We genotyped a total of 21 tagging single nucleotide polymorphisms spanning the IGF2BP2 locus in our type 2 diabetes case-control cohort comprising 3,093 French Caucasian subjects.

Results: IGF2BP2 variants rs4402960 and rs1470579 were not associated with type 2 diabetes in the present study (P = 0.632 and P = 0.896, respectively). Meta-analysis of genotype data from over 34,000 subjects demonstrated that our inability to replicate rs4402960/rs1470579 was consistent with the findings from several previous genome-wide association study (GWAS) datasets that were underpowered to detect this modest association signal (odds ratio [OR] 1.14). We obtained novel evidence that rs9826022, a borderline rare variant (5% minor allele frequency) in the 3' downstream region, was associated with type 2 diabetes (P = 0.0002; OR 1.53 [95% CI 1.22-1.91]). This result was corroborated by the meta-analysis of 10,542 genotypes from the current study and GWAS datasets using both fixed (P = 9.47 x 10(-6); 1.30 [1.16-1.46]) and random effects (P = 0.001; 1.30 [1.11-1.52)] calculations.

Conclusions: We were unable to replicate the confirmed rs4402960/rs1470579 susceptibility variants but found novel evidence for a rare variant in the 3' downstream region of IGF2BP2. Further genetic and functional studies are required to identify the etiological IGF2BP2 variants.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Canada
  • Diabetes Mellitus, Type 2 / genetics*
  • Family
  • Female
  • France / ethnology
  • Genetic Predisposition to Disease
  • Genetic Variation*
  • Genome, Human
  • Humans
  • Male
  • Middle Aged
  • Odds Ratio
  • Polymorphism, Single Nucleotide*
  • RNA-Binding Proteins / genetics*
  • White People / genetics

Substances

  • IGF2BP2 protein, human
  • RNA-Binding Proteins