IGF2BP2 and IGF2 genetic effects in diabetes and diabetic nephropathy
Language English Country United States Media print-electronic
Document type Journal Article, Research Support, Non-U.S. Gov't
PubMed
22770937
DOI
10.1016/j.jdiacomp.2012.05.012
PII: S1056-8727(12)00166-3
Knihovny.cz E-resources
- MeSH
- Diabetes Mellitus, Type 1 complications genetics metabolism MeSH
- Diabetes Mellitus, Type 2 complications genetics metabolism MeSH
- Diabetic Nephropathies complications genetics metabolism MeSH
- Genetic Association Studies MeSH
- Insulin-Like Growth Factor II genetics metabolism MeSH
- Polymorphism, Single Nucleotide * MeSH
- Cohort Studies MeSH
- Kidney growth & development metabolism MeSH
- Humans MeSH
- Mice, Mutant Strains MeSH
- Mice MeSH
- Sex Characteristics MeSH
- RNA-Binding Proteins genetics metabolism MeSH
- Gene Expression Regulation MeSH
- Animals MeSH
- Check Tag
- Humans MeSH
- Male MeSH
- Mice MeSH
- Female MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Geographicals
- Czech Republic MeSH
- United States MeSH
- Sweden MeSH
- Names of Substances
- IGF2 protein, human MeSH Browser
- IGF2 protein, mouse MeSH Browser
- IGF2BP2 protein, human MeSH Browser
- IGF2BP2 protein, mouse MeSH Browser
- Insulin-Like Growth Factor II MeSH
- RNA-Binding Proteins MeSH
OBJECTIVE: 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. MATERIALS AND METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.
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