Department of Molecular Medicine and Surgery, Rolf Luft Research Center for Diabetes and Endocrinology, Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden.
J Diabetes Complications. 2012 Sep-Oct;26(5):393-8. doi: 10.1016/j.jdiacomp.2012.05.012. Epub 2012 Jul 4.
The 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.
Three 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 26 weeks was examined with real time RT-PCR and Western blot.
An 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 26 weeks.
The 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.
IGF2BP2 基因位于染色体 3q27.2 上，该区域与 1 型糖尿病（T1D）、2 型糖尿病（T2D）和糖尿病肾病（DN）有关。其蛋白可与印迹 IGF2 基因的 5'-UTR 结合。本研究旨在评估 IGF2BP2-IGF2 基因在糖尿病和 DN 中的遗传效应。
本研究纳入了来自 GoKinD 研究的 T1D 合并或不合并 DN（n=1139）、瑞典 T1D 合并或不合并 DN（n=303）以及捷克无糖尿病、T1D、T2D 的对照组受试者，采用 TaqMan 基因分型实验检测 IGF2BP2 rs4402960 和 IGF2 rs10770125。采用实时 RT-PCR 和 Western blot 检测 5 周和 26 周龄 db/db 小鼠和对照小鼠肾脏组织中 Igf2bp2 基因的表达。
在捷克人群中，IGF2BP2 rs4402960 与 T2D 的关联得到了复制。该 IGF2BP2 多态性（P=0.037，OR=0.69，95%CI 0.49-0.98）与 GoKinD 研究中选择的 T1D 男性患者的 DN 相关，而与女性患者无关。在对 GoKinD、捷克和瑞典人群的综合分析中，IGF2BP2 多态性与 T1D 男性患者的 DN 仍存在显著相关性（P=0.030，OR=0.73，95%CI 0.54-0.97）。IGF2 rs10770125 也与 GoKinD 人群中 T1D 男性患者的 DN 相关（P=0.038，OR=0.67，95%CI 0.46-0.98）。IGF2BP2 和 IGF2 之间可能存在遗传相互作用（P=0.05）。与对照组相比，db/db 小鼠肾脏组织中的 Igf2bp2 基因表达水平在 5 周时升高，但在 26 周时无差异。
本研究在捷克人群中复制了 IGF2BP2 rs4402960 与 T2D 的关联，并提供了数据表明，IGF2BP2 可能与 IGF2 存在遗传相互作用，对 T1D 男性患者的 DN 具有保护作用。
