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Published online April 22, 2008
Diabetes 57:1992-1996, 2008
DOI: 10.2337/db07-1789
© 2008 by the American Diabetes Association
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Brief Report

Evaluation of the Association of IGF2BP2 Variants With Type 2 Diabetes in French Caucasians

Konsta Duesing1, Ghazaleh Fatemifar1, Guillaume Charpentier2, Michel Marre3,4, Jean Tichet5, Serge Hercberg6, Beverley Balkau7,8, Philippe Froguel1,9, and Fernando Gibson1

1 Section of Genomic Medicine, Imperial College London, Hammersmith Campus, London, U.K
2 Endocrinology-Diabetology Unit, Corbeil Hospital, Corbeil, France
3 Endocrinology-Diabetology Unit, Bichat Hospital, Paris, France
4 INSERM U695, Paris, France
5 Institut Régional Pour la Santé, Tours, France
6 INSERM U557/U1125 Inra/Cnam/University Paris, Bobigny, France
7 INSERM U780-IFR69, Villejuif, France
8 Paris Univ-Sud, Orsay, France
9 CNRS 8090, Institut de Biologie de Lille, Institut Pasteur, Lille, France

Corresponding author: Fernando Gibson, fernando.gibson{at}imperial.ac.uk

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.


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