Evaluation of the association of IGF2BP2 variants with type 2 diabetes in French Caucasians.
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.
Duesing
Konsta
K
Section of Genomic Medicine, Imperial College London, Hammersmith Campus, London, U.K.
Fatemifar
Ghazaleh
G
Charpentier
Guillaume
G
Marre
Michel
M
Tichet
Jean
J
Hercberg
Serge
S
Balkau
Beverley
B
Froguel
Philippe
P
Gibson
Fernando
F
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
C498779:IGF2BP2 protein, human; D016601:RNA-Binding Proteins