biostudies-literatureUnknown2023Pang SType 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.International journal of endocrinology6919275https://www.ebi.ac.uk/biostudies/studies/S-EPMC9899147biostudies-literatureGenetic Variants of <i>SIRT1</i> Gene Promoter in Type 2 Diabetes.PMC9899147Pang SZhang ZZhang JYan BZhou YfalseGenetic Variants of <i>SIRT1</i> Gene Promoter in Type 2 Diabetes.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.2023-01-01T00:00:00Z20232025-04-29T09:50:59.011Z2025-04-06T19:11:08.545ZS-EPMC98991473674799510.1155/2023/6919275