{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"omics_type":["Unknown"],"volume":["2023"],"submitter":["Pang S"],"pubmed_abstract":["Type 2 diabetes (T2D) is a highly heterogeneous and polygenic disease. To date, genetic causes and underlying mechanisms for T2D remain unclear. SIRT1, one member of highly conserved NAD-dependent class III deacetylases, has been implicated in many human diseases. Accumulating evidence indicates that SIRT1 is involved in insulin resistance and impaired pancreatic <i>β</i>-cell function, the two hallmarks of T2D. Thus, we speculated that altered SIRT1 levels, resulting from the genetic variants within its regulatory region of <i>SIRT1</i> gene, may contribute to the T2D development. In this study, the <i>SIRT1</i> gene promoter was genetically analyzed in T2D patients (<i>n</i> = 218) and healthy controls (<i>n</i> = 358). A total of 20 genetic variants, including 7 single-nucleotide polymorphisms (SNPs), were identified. Five heterozygous genetic variants (g.4114-15InsA, g.4801G > A, g.4816G > C, g.4934G > T, and g.4963_64Ins17bp) and one SNP (g.4198A > C (rs35706870)) were identified in T2D patients, but in none of the controls. The frequencies of two SNPs (g.4540A > G (rs3740051) (OR: 1.75, 95% CI: 1.24-2.47, <i>P</i> < 0.001 in dominant genetic model) and g.4821G > T (rs35995735)) (OR: 3.58, 95% CI: 1.94-6.60, <i>P</i> < 0.001 in dominant genetic model) were significantly higher in T2D patients. Further association and haplotype analyses confirmed that these two SNPs were strongly linked, contributing to the T2D (OR: 1.442, 95% CI: 1.080-1.927, <i>P</i> < 0.05). Moreover, most of the genetic variants identified in T2D were disease-specific. Taken together, the genetic variants within <i>SIRT1</i> gene promoter might contribute to the T2D development by altering SIRT1 levels. Underlying molecular mechanism needs to be further explored."],"journal":["International journal of endocrinology"],"pagination":["6919275"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC9899147"],"repository":["biostudies-literature"],"pubmed_title":["Genetic Variants of <i>SIRT1</i> Gene Promoter in Type 2 Diabetes."],"pmcid":["PMC9899147"],"pubmed_authors":["Pang S","Zhang Z","Zhang J","Yan B","Zhou Y"],"additional_accession":[]},"is_claimable":false,"name":"Genetic Variants of <i>SIRT1</i> Gene Promoter in Type 2 Diabetes.","description":"Type 2 diabetes (T2D) is a highly heterogeneous and polygenic disease. To date, genetic causes and underlying mechanisms for T2D remain unclear. SIRT1, one member of highly conserved NAD-dependent class III deacetylases, has been implicated in many human diseases. Accumulating evidence indicates that SIRT1 is involved in insulin resistance and impaired pancreatic <i>β</i>-cell function, the two hallmarks of T2D. Thus, we speculated that altered SIRT1 levels, resulting from the genetic variants within its regulatory region of <i>SIRT1</i> gene, may contribute to the T2D development. In this study, the <i>SIRT1</i> gene promoter was genetically analyzed in T2D patients (<i>n</i> = 218) and healthy controls (<i>n</i> = 358). A total of 20 genetic variants, including 7 single-nucleotide polymorphisms (SNPs), were identified. Five heterozygous genetic variants (g.4114-15InsA, g.4801G > A, g.4816G > C, g.4934G > T, and g.4963_64Ins17bp) and one SNP (g.4198A > C (rs35706870)) were identified in T2D patients, but in none of the controls. The frequencies of two SNPs (g.4540A > G (rs3740051) (OR: 1.75, 95% CI: 1.24-2.47, <i>P</i> < 0.001 in dominant genetic model) and g.4821G > T (rs35995735)) (OR: 3.58, 95% CI: 1.94-6.60, <i>P</i> < 0.001 in dominant genetic model) were significantly higher in T2D patients. Further association and haplotype analyses confirmed that these two SNPs were strongly linked, contributing to the T2D (OR: 1.442, 95% CI: 1.080-1.927, <i>P</i> < 0.05). Moreover, most of the genetic variants identified in T2D were disease-specific. Taken together, the genetic variants within <i>SIRT1</i> gene promoter might contribute to the T2D development by altering SIRT1 levels. Underlying molecular mechanism needs to be further explored.","dates":{"release":"2023-01-01T00:00:00Z","publication":"2023","modification":"2025-04-29T09:50:59.011Z","creation":"2025-04-06T19:11:08.545Z"},"accession":"S-EPMC9899147","cross_references":{"pubmed":["36747995"],"doi":["10.1155/2023/6919275"]}}