Evaluation of the Association of IGF2BP2 Variants With Type 2 Diabetes in French Caucasians
Author:
Duesing Konsta1, Fatemifar Ghazaleh1, Charpentier Guillaume2, Marre Michel34, Tichet Jean5, Hercberg Serge6, Balkau Beverley78, Froguel Philippe19, Gibson Fernando1
Affiliation:
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
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 × 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.
Publisher
American Diabetes Association
Subject
Endocrinology, Diabetes and Metabolism,Internal Medicine
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