Common Variants in IGF2BP2 Gene rs4402960 and rs1470579 Polymorphisms Associate with Type 2 Diabetes Mellitus in Egyptians: A Replication Study

摘要

Genome-wide association studies identified novel genes associated with T2DM which have been replicated in different ethnic populations and yielded inconsistent results. Our study aimed to replicate in Egyptian population the identified association of insulin growth factor 2 m-RNA binding protein 2 (IGF2BP2) genetic variants rs4402960 and rs1470579 with T2DM. Our study included 120 unrelated T2DM patients and 128 control subjects who were genotyped by real-time polymerase chain reaction (real-time PCR). For rs1470579, the variant C allele was associated with T2DM (p<0.001). The frequency of (A/C + C/C) genotypes vs. A/A genotype was significantly higher in T2DM patients than in controls (70% vs. 30% and 37.5% vs. 62.5%, respectively) (p=0.00001). For rs440960, the variant T allele was associated with T2DM (p<0.001). Genotype G/G was the most frequent in controls (62.5%). The frequency of (G/T + T/T) genotypes vs. G/G genotype was significantly higher in T2DM patients than in controls (65.5% vs. 34.5% and 37.5% vs. 62.5%, respectively), (p=0.00001). These associations remained significant under all genetic models and after adjustment for covariates: gender, BMI, TGs and HDL-c. Both SNPs were in strong LD (D′ = 0.99 and r~(2) =0.98). Taking the common GA haplotype as reference, TC was the most frequent haplotype in T2DM patients and strongly associated with the disease (p = 0.004, OR= 3.29, 95%CI = 2.19–10.84), followed by GC haplotype (p = 0.02, OR=1.42, 95% CI=1.08–1.88) then the TA haplotype (P= 0.04, OR=1.14, 95%CI=0.99–1.86). In conclusion, IGF2BP2 susceptibility variants rs4402960 and rs1470579 associate with T2DM in Egyptians.