Association between single nucleotide polymorphisms within genes encoding sirtuin families and diabetic nephropathy in Japanese subjects with type 2 diabetes
- نوع فایل : کتاب
- زبان : انگلیسی
- مؤلف : Shiro Maeda Daisuke Koya Shin-ichi Araki Tetsuya Babazono Tomoya Umezono Masao Toyoda Koichi Kawai Masahito Imanishi Takashi Uzu Dai
- چاپ و سال / کشور: 2011
Description
Background Sirtuin is a member of the nicotinamide adenine dinucleotide (NAD)-dependent deacetylases, and has been reported to play a pivotal role in energy expenditure, mitochondrial function and pathogenesis of metabolic diseases, including aging kidneys. In this study, we focused on the genes encoding sirtuin families, and examined the association between single nucleotide polymorphisms (SNPs) within genes encoding sirtuin families and diabetic nephropathy. Methods We examined 52 SNPs within the SIRT genes (11 in SIRT1, 7 in SIRT2, 14 in SIRT3, 7 in SIRT4, 9 in SIRT5, and 4 in SIRT6) in 3 independent Japanese populations with type 2 diabetes (study 1: 747 cases (overt proteinuria), 557 controls; study 2: 455 cases (overt proteinuria) and 965 controls; study 3: 300 cases (end-stage renal disease) and 218 controls). The associations between these SNPs were analyzed by the Cochran–Armitage trend test, and results of the 3 studies were combined with a meta-analysis. We further examined an independent cohort (195 proteinuria cases and 264 controls) for validation of the original association. Results We identified 4 SNPs in SIRT1 that were nominally associated with diabetic nephropathy (P\0.05), and subsequent haplotype analysis revealed that a haplotype consisting of the 11 SNPs within SIRT1 locus had a stronger association (P = 0.0028). Conclusion These results indicate that SIRT1 may play a role in susceptibility to diabetic nephropathy in Japanese subjects with type 2 diabetes
Clin Exp Nephrol (2011) 15:381–390 Received: 21 July 2010 / Accepted: 19 January 2011 / Published online: 18 February 2011 Japanese Society of Nephrology 2011
