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Diabetes Publish Ahead of Print published online ahead of print April 22, 2008
DOI: 10.2337/db07-1789
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Original Research

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

1Genomic Medicine, Imperial College London, Hammersmith Campus, Du Cane Rd, London W12 0NN, UK
2Endocrinology-Diabetology Unit, Corbeil Hospital, Corbeil, France
3Endocrinology-Diabetology, Bichat Hospital, Paris, France
4INSERM U695, Paris, France
5Institut Régional Pour la Santé, Tours, France
6U557 Inserm/U1125 Inra/Cnam/University Paris 13, CRNH IdF, F-93017 Bobigny, France
7INSERM U780-IFR69, Villejuif, France
8Paris Univ-Sud, Orsay, France
9CNRS 8090, Institut de Biologie de Lille, Institut Pasteur, CHU Lille, France

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 characterise the susceptibility variants at this novel locus.

Research Design and Methods: We genotyped a total of 21 tagging SNPs spanning the IGF2BP2 locus in our type 2 diabetes case-control cohort comprising in 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 GWAS datasets that were under-powered to detect this modest association signal (OR 1.14). We obtained novel evidence that rs9826022, a borderline rare variant (5% MAF) 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; OR 1.30 [95% CI 1.16-1.46]) and random effects (P = 0.001; 1.30 [95 %CI 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 aetiological IGF2BP2 variants.

Correspondence: fernando.gibson{at}imperial.ac.uk


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