Insulin-like Growth Factor 2 Binding Protein 2 Gene Polymorphism in Egyptian Patients with Type 2 Diabetes

Abstract

Genome-wide association studies (GWAS) identified novel genes associated with type 2 diabetes mellitus (T2DM) which have been replicated in different ethnic populations and yielded inconsistent results. The insulin-like growth factor mRNA-2 binding protein 2 (IGF2BP2) is highly expressed in pancreatic islets, which play roles in normal embryonic growth and development. Our study aimed to replicate the association between insulin growth factor 2 mRNA binding protein 2 (IGF2BP2) gene (rs4402960) variant and T2DM in Egyptian diabetic patients resident in Ismailia city. The study included 152 subjects (76 unrelated T2DM patients and 76 control subjects) who were genotyped by polymerase chain reaction-restriction fragment length polymorphism technique (PCR- RFLP). Age, sex, blood pressure, BMI and Waist Circumference were recorded, and blood glucose, serum triglyceride, total cholesterol (TC), low-density lipoprotein-cholesterol (LDL-C), high-density lipoprotein-cholesterol (HDL-C) and homeostatic model assessment (HOMA) indices were determined. Fasting serum insulin and IGF2BP2 protein levels were analyzed by ELISA. For rs440960 variant of IGF2BP2 gene, risk allele T frequency was associated with T2DM [OR (95% CI)=1.82 (1.14- 2.93), P= 0.012]. The frequency of T/T genotype versus (GG+G/T) genotypes was significantly higher in T2DM patients compared to controls (22.4% vs. 77.6% and 5.3% vs. 94.7%, respectively), (P=0.002). This association remained significant under additive (P=0.003) and co-dominant (P=0.009) genetic models. From this study, it could be concluded that IGF2BP2 rs4402960 polymorphism was found to be significantly associated with the increased risk of T2DM.

Keywords: Type 2 diabetes mellitus, Single nucleotide polymorphism, IGF2BP2.