Strong association of common variants in the IGF2BP2 gene with type 2 diabetes in Lebanese Arabs

Abstract

Objective: Several genome-wide association studies and replication analyses have identified common variation at the insulin-like binding protein 2 (IGF2BP2) gene to be associated with type 2 diabetes (T2DM). The aim of this study was to replicate in a Lebanese Arab population identified associations of IGF2BP2 variants rs4402960 and rs1470579 with T2DM.

Methods: This case-control study involved 544 T2DM patients and 606 control subjects. Genotyping was done by the allelic exclusion method.

Results: T allele of rs440960 (P=6.5 × 10(-6)) and C allele of rs1470579 (P=5.3 × 10(-4)) were significantly associated with T2DM; both SNPs were in strong LD (D'=0.83, r(2)=0.58). While both IGF2BP2 SNPs were significantly associated with T2DM under additive and recessive models, only rs4402960 remained significantly associated with T2DM under the dominant model. Taking the common rs4402960/rs1470579 GA haplotype as reference, multivariate analysis confirmed the positive association of TC (P=0.009; OR, 1.43; 95%CI, 1.09-1.87), and TA (P<0.001; OR=5.49; 95%CI=2.09-14.39) haplotypes with increased T2DM risk. These differences remained significant after applying the Bonferroni correction for multiple testing.

Conclusion: We validate that IGF2BP2 susceptibility variants rs4402960 and rs1470579 associate with T2DM in Lebanese Arabs.