Type 2 diabetes-associated polymorphisms correlate with SIRT1 and TGF-β1 gene expression.

Publisher: Wiley-Blackwell Country of Publication: England NLM ID: 0416661 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1469-1809 (Electronic) Linking ISSN: 00034800 NLM ISO Abbreviation: Ann Hum Genet Subsets: MEDLINE

Publication: <2010-> : Oxford : Wiley-Blackwell
Original Publication: Oxford : Blackwell

Genetic Predisposition to Disease* ; Polymorphism, Single Nucleotide*; Biomarkers/*analysis ; Diabetes Mellitus, Type 2/*genetics ; Diabetes Mellitus, Type 2/*pathology ; Sirtuin 1/*genetics ; Transforming Growth Factor beta1/*genetics; Female ; Genotype ; Humans ; Linkage Disequilibrium ; Male ; Middle Aged ; Prognosis

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.
(© 2019 John Wiley & Sons Ltd/University College London.)

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FIS/IMSS/PROT/G14/1333 International Instituto Mexicano del Seguro Social

Keywords: SIRT1; TGF-β1; diabetes; rs1800470; rs3758391; rs932658

0 (Biomarkers)
0 (TGFB1 protein, human)
0 (Transforming Growth Factor beta1)
EC 3.5.1.- (SIRT1 protein, human)
EC 3.5.1.- (Sirtuin 1)

Date Created: 20191205 Date Completed: 20210204 Latest Revision: 20210204

20240628

10.1111/ahg.12363

31799723