Association between single nucleotide polymorphisms within genes encoding sirtuin families and diabetic nephropathy in Japanese subjects with type 2 diabetes

被引：61

作者：

Maeda, Shiro ^{[1
]}

Koya, Daisuke ^{[2
]}

Araki, Shin-ichi ^{[3
]}

Babazono, Tetsuya ^{[4
]}

Umezono, Tomoya ^{[5
]}

Toyoda, Masao ^{[5
]}

Kawai, Koichi ^{[6
]}

Imanishi, Masahito ^{[7
]}

Uzu, Takashi ^{[3
]}

Suzuki, Daisuke ^{[5
]}

Maegawa, Hiroshi ^{[3
]}

Kashiwagi, Atsunori ^{[3
]}

Iwamoto, Yasuhiko ^{[4
]}

Nakamura, Yusuke ^{[8
]}

机构：

[1] RIKEN Ctr Genom Med, Lab Endocrinol & Metab, Tsurumi Ku, Kanagawa 2300045, Japan

[2] Kanazawa Med Univ, Div Endocrinol & Metab, Kanazawa, Ishikawa, Japan

[3] Shiga Univ Med Sci, Dept Med, Shiga, Japan

[4] Tokyo Womens Med Univ, Ctr Diabet, Tokyo, Japan

[5] Tokai Univ, Div Nephrol & Metab, Dept Internal Med, Sch Med, Kanagawa 2591100, Japan

[6] Kawai Clin, Ibaraki, Japan

[7] Osaka City Gen Hosp, Dept Internal Med, Osaka, Japan

[8] Univ Tokyo, Mol Med Lab, Ctr Human Genome, Inst Med Sci, Tokyo 1088639, Japan

来源：

CLINICAL AND EXPERIMENTAL NEPHROLOGY | 2011年 / 15卷 / 03期

关键词：

Single nucleotide polymorphism (SNP); Association study; SIRT1; Diabetic nephropathy; GENOME-WIDE ASSOCIATION; SUSCEPTIBILITY; RESTRICTION; COMPLICATIONS; MELLITUS; DISEASE; KIDNEY;

D O I：

10.1007/s10157-011-0418-0

中图分类号：

R5 [内科学]; R69 [泌尿科学（泌尿生殖系疾病）];

学科分类号：

1002 ; 100201 ;

摘要：

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. 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. 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). These results indicate that SIRT1 may play a role in susceptibility to diabetic nephropathy in Japanese subjects with type 2 diabetes.

引用

页码：381 / 390

页数：10

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