Type 2 diabetes-associated polymorphisms correlate with SIRT1 and TGF-β1 gene expression
| Autor: | Fernando Suarez-Sanchez, Jaime Gómez, Jesus Peralta, Miguel Vázquez-Moreno, Miguel Cruz, Ángeles Ramírez, Clara Ortega, Adán Valladares, Miriam Hernández, Rocío Suárez-Sánchez |
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| Rok vydání: | 2019 |
| Předmět: |
Male
Linkage disequilibrium Genotype Single-nucleotide polymorphism Biology Polymorphism Single Nucleotide Linkage Disequilibrium Transforming Growth Factor beta1 03 medical and health sciences Sirtuin 1 Gene expression Genetics TaqMan Humans Electrophoretic mobility shift assay Genetic Predisposition to Disease Nuclear protein Gene Genetics (clinical) 030304 developmental biology 0303 health sciences 030305 genetics & heredity Middle Aged Prognosis Molecular biology Diabetes Mellitus Type 2 Female Biomarkers |
| Zdroj: | Annals of human geneticsREFERENCES. 84(2) |
| ISSN: | 1469-1809 |
| Popis: | The polymorphisms rs3758391 and rs1800470 located in SIRT1 and TGF-β1 have been associated with type 2 diabetes in different populations but its functional effect is not clear. In this study, we evaluated their effect on the expression of SIRT1 and TGF-β1 in peripheral blood as well as their participation in the formation of DNA-protein complexes in a pancreas-derived cell line. It has been described that SIRT1 and TGF-β1 participate in cell growth and regulation of production and secretion of insulin in the pancreas. Anthropometric and biochemical profiles of 127 adults were measured. Genotypes for rs3758391 and rs1800470 were determined using TaqMan assays. Expression analysis of SIRT1 and TGF-β1 were performed using real-time PCR. Gene expression of these genes increased 1.8 ± 0.6- and 1.3 ± 0.6-fold in patients carrying the TT genotype of rs3758391 and rs1800470 when compared to carriers of the CC genotype. Then, we tested whether these single-nucleotide polymorphisms (SNPs) (and rs932658, which is in linkage disequilibrium with rs3758391) are located in regulatory DNA-protein binding sites by electrophoretic mobility shift assays using nuclear extract from the pancreas-derived cell line BxPC-3. The electrophoretic mobility shift assay showed no binding of nuclear proteins to DNA. In conclusion, the genotypes of rs3758391 and rs1800470 are associated with modifications in the expression of the genes SIRT1 and TGF-β1, respectively, but none of the tested SNPs are located in regulatory DNA-protein binding sites. |
| Databáze: | OpenAIRE |
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