title: Association between single nucleotide polymorphisms within genes encoding sirtuin families and diabetic nephropathy in Japanese subjects with type 2 diabetes.
abstract: 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).
  
  
  CONCLUSIONS
  These results indicate that SIRT1 may play a role in susceptibility to diabetic nephropathy in Japanese subjects with type 2 diabetes.
authors.affiliation: Laboratory for Endocrinology and Metabolism, RIKEN Center for Genomic Medicine, 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama, Kanagawa, 230-0045, Japan. smaeda@src.riken.jp.
authors.forename: Shiro
authors.initials: S
authors.lastname: Maeda
authors.affiliation: Division of Endocrinology and Metabolism, Kanazawa Medical University, Ishikawa, Japan.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Koya
authors.affiliation: Department of Medicine, Shiga University of Medical Science, Otsu, Shiga, Japan.
authors.forename: Shin-Ichi
authors.initials: SI
authors.lastname: Araki
authors.affiliation: The Diabetes Center, Tokyo Women's Medical University, Tokyo, Japan.
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Babazono
authors.affiliation: Division of Nephrology and Metabolism, Department of Internal Medicine, Tokai University School of Medicine, Isehara, Kanagawa, Japan.
authors.forename: Tomoya
authors.initials: T
authors.lastname: Umezono
authors.affiliation: Division of Nephrology and Metabolism, Department of Internal Medicine, Tokai University School of Medicine, Isehara, Kanagawa, Japan.
authors.forename: Masao
authors.initials: M
authors.lastname: Toyoda
authors.affiliation: Kawai Clinic, Ibaraki, Japan.
authors.forename: Koichi
authors.initials: K
authors.lastname: Kawai
authors.affiliation: Department of Internal Medicine, Osaka City General Hospital, Osaka, Japan.
authors.forename: Masahito
authors.initials: M
authors.lastname: Imanishi
authors.affiliation: Department of Medicine, Shiga University of Medical Science, Otsu, Shiga, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Uzu
authors.affiliation: Division of Nephrology and Metabolism, Department of Internal Medicine, Tokai University School of Medicine, Isehara, Kanagawa, Japan.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Suzuki
authors.affiliation: Department of Medicine, Shiga University of Medical Science, Otsu, Shiga, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Maegawa
authors.affiliation: Department of Medicine, Shiga University of Medical Science, Otsu, Shiga, Japan.
authors.forename: Atsunori
authors.initials: A
authors.lastname: Kashiwagi
authors.affiliation: The Diabetes Center, Tokyo Women's Medical University, Tokyo, Japan.
authors.forename: Yasuhiko
authors.initials: Y
authors.lastname: Iwamoto
authors.affiliation: Laboratory of Molecular Medicine, Human Genome Center, Institute of Medical Science, University of Tokyo, Tokyo, 108-8639, Japan.
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Nakamura
mesh_terms: D044466:Asian People / Q000235:genetics; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics*; D003928:Diabetic Nephropathies / Q000235:genetics*; D005787:Gene Frequency; D006801:Humans; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D056564:Sirtuin 1 / Q000235:genetics*; D037761:Sirtuins / Q000235:genetics
chemical_list: C447939:SIRT1 protein, human; D056564:Sirtuin 1; D037761:Sirtuins