Genetic Variants of SIRT1 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 tha...
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| Format: | Article |
| Language: | English |
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Wiley
2023-01-01
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| Series: | International Journal of Endocrinology |
| Online Access: | http://dx.doi.org/10.1155/2023/6919275 |
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| author | Shuchao Pang Zhengjun Zhang Yu Zhou Jie Zhang Bo Yan |
| author_facet | Shuchao Pang Zhengjun Zhang Yu Zhou Jie Zhang Bo Yan |
| author_sort | Shuchao Pang |
| collection | DOAJ |
| 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 β-cell function, the two hallmarks of T2D. Thus, we speculated that altered SIRT1 levels, resulting from the genetic variants within its regulatory region of SIRT1 gene, may contribute to the T2D development. In this study, the SIRT1 gene promoter was genetically analyzed in T2D patients (n = 218) and healthy controls (n = 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, P<0.001 in dominant genetic model) and g.4821G > T (rs35995735)) (OR: 3.58, 95% CI: 1.94–6.60, P<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, P<0.05). Moreover, most of the genetic variants identified in T2D were disease-specific. Taken together, the genetic variants within SIRT1 gene promoter might contribute to the T2D development by altering SIRT1 levels. Underlying molecular mechanism needs to be further explored. |
| format | Article |
| id | doaj-art-18c01020b0a242d4a938ff2c90fccf75 |
| institution | Kabale University |
| issn | 1687-8345 |
| language | English |
| publishDate | 2023-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | International Journal of Endocrinology |
| spelling | doaj-art-18c01020b0a242d4a938ff2c90fccf752025-02-03T06:08:46ZengWileyInternational Journal of Endocrinology1687-83452023-01-01202310.1155/2023/6919275Genetic Variants of SIRT1 Gene Promoter in Type 2 DiabetesShuchao Pang0Zhengjun Zhang1Yu Zhou2Jie Zhang3Bo Yan4Shandong Provincial Sino-US Cooperation Research Center for Translational MedicineDivision of EndocrinologyShandong Provincial Sino-US Cooperation Research Center for Translational MedicineCardiovascular CenterShandong Provincial Sino-US Cooperation Research Center for Translational MedicineType 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 β-cell function, the two hallmarks of T2D. Thus, we speculated that altered SIRT1 levels, resulting from the genetic variants within its regulatory region of SIRT1 gene, may contribute to the T2D development. In this study, the SIRT1 gene promoter was genetically analyzed in T2D patients (n = 218) and healthy controls (n = 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, P<0.001 in dominant genetic model) and g.4821G > T (rs35995735)) (OR: 3.58, 95% CI: 1.94–6.60, P<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, P<0.05). Moreover, most of the genetic variants identified in T2D were disease-specific. Taken together, the genetic variants within SIRT1 gene promoter might contribute to the T2D development by altering SIRT1 levels. Underlying molecular mechanism needs to be further explored.http://dx.doi.org/10.1155/2023/6919275 |
| spellingShingle | Shuchao Pang Zhengjun Zhang Yu Zhou Jie Zhang Bo Yan Genetic Variants of SIRT1 Gene Promoter in Type 2 Diabetes International Journal of Endocrinology |
| title | Genetic Variants of SIRT1 Gene Promoter in Type 2 Diabetes |
| title_full | Genetic Variants of SIRT1 Gene Promoter in Type 2 Diabetes |
| title_fullStr | Genetic Variants of SIRT1 Gene Promoter in Type 2 Diabetes |
| title_full_unstemmed | Genetic Variants of SIRT1 Gene Promoter in Type 2 Diabetes |
| title_short | Genetic Variants of SIRT1 Gene Promoter in Type 2 Diabetes |
| title_sort | genetic variants of sirt1 gene promoter in type 2 diabetes |
| url | http://dx.doi.org/10.1155/2023/6919275 |
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