Evaluation of the association of IGF2BP2 variants with type 2 diabetes in French Caucasians
| Autor: | Michel Marre, Serge Hercberg, Konsta Duesing, Philippe Froguel, Guillaume Charpentier, Jean Tichet, Beverley Balkau, Ghazaleh Fatemifar, Fernando Gibson |
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| Rok vydání: | 2008 |
| Předmět: |
Male
Canada Endocrinology Diabetes and Metabolism 030209 endocrinology & metabolism Single-nucleotide polymorphism Genome-wide association study Locus (genetics) Type 2 diabetes Biology Polymorphism Single Nucleotide White People 03 medical and health sciences 0302 clinical medicine Genotype Internal Medicine medicine Odds Ratio Genetics Humans Family Genetic Predisposition to Disease 030304 developmental biology Genetic association Aged 0303 health sciences Genome Human Genetic Variation RNA-Binding Proteins Odds ratio Middle Aged medicine.disease 3. Good health Minor allele frequency Diabetes Mellitus Type 2 Female France |
| Zdroj: | Diabetes |
| ISSN: | 1939-327X |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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