IGF2BP2 and IGF2 genetic effects in diabetes and diabetic nephropathy

Abstract

ObjectiveThe IGF2BP2 gene is located on chromosome 3q27.2 within a region linked to type 1 diabetes (T1D), type 2 diabetes (T2D) and diabetic nephropathy (DN). Its protein functionally binds to 5’-UTR of the imprinting IGF2 gene. The present study aims to evaluate the IGF2BP2-IGF2 genetic effects in diabetes and DN. Materials and MethodsThree cohorts including T1D with and without DN (n=1139) of European descents from the GoKinD study, Swedish T1D with and without DN (n=303) and Czech control subjects without diabetes, T1D, T2D with and without DN (n=1418) were enrolled in TaqMan genotyping experiments for IGF2BP2 rs4402960 and IGF2 rs10770125. Igf2bp2 gene expression in kidney tissues of db/db and control mice at the ages of 5 and 26weeks was examined with real time RT-PCR and Western blot. ResultsAn association of IGF2BP2 rs4402960 with T2D in the Czech population was replicated. This IGF2BP2 polymorphism (P=0.037, OR=0.69 95% CI 0.49–0.98) was found to be associated with DN in male not in female patients with T1D selected from the GoKinD study. In the analyses of combined the GoKinD, Czech and Swedish populations, the association between IGF2BP2 polymorphism and DN in male patients with T1D was still significant (P=0.030, OR=0.73, 95% CI 0.54–0.97). IGF2 rs10770125 was also associated with DN in male T1D patients of the GoKinD population (P=0.038, OR=0.67 95% CI 0.46–0.98). There might be a genetic interaction between IGF2BP2 and IGF2 (P=0.05). The Igf2bp2 gene expression levels were increased in the kidneys of db/db mice compared to controls at the age of 5weeks but not at 26weeks. ConclusionsThe present study has replicated the association of IGF2BP2 rs4402960 with T2D in the Czech population and provided data suggesting that IGF2BP2 may have genetic interaction with IGF2 with a protective effect against DN in male patients with T1D.