title: Evaluation of the association of IGF2BP2 variants with type 2 diabetes in French Caucasians.
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.
  
  
  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.
authors.affiliation: Section of Genomic Medicine, Imperial College London, Hammersmith Campus, London, U.K.
authors.forename: Konsta
authors.initials: K
authors.lastname: Duesing
authors.forename: Ghazaleh
authors.initials: G
authors.lastname: Fatemifar
authors.forename: Guillaume
authors.initials: G
authors.lastname: Charpentier
authors.forename: Michel
authors.initials: M
authors.lastname: Marre
authors.forename: Jean
authors.initials: J
authors.lastname: Tichet
authors.forename: Serge
authors.initials: S
authors.lastname: Hercberg
authors.forename: Beverley
authors.initials: B
authors.lastname: Balkau
authors.forename: Philippe
authors.initials: P
authors.lastname: Froguel
authors.forename: Fernando
authors.initials: F
authors.lastname: Gibson
mesh_terms: D000368:Aged; D002170:Canada; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics*; D005190:Family; D005260:Female; D005602:France / Q000208:ethnology; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D015894:Genome, Human; D006801:Humans; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide; D016601:RNA-Binding Proteins / Q000235:genetics*; D044465:White People / Q000235:genetics
chemical_list: C498779:IGF2BP2 protein, human; D016601:RNA-Binding Proteins