慢性腎臓病の早期発見と末期腎不全・心血管障害予防のための個別化予防システムの開発

2014 Fiscal Year Annual Research Report

• Project/Area Number: 24590746
• Research Institution: Mie University
• Principal Investigator: 山田 芳司 三重大学, 生命科学研究支援センター, 教授 (90333286)
• Co-Investigator(Kenkyū-buntansha): 西田 有 三重大学, 生命科学研究支援センター, 助教 (50287463)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Keywords: 慢性腎臓病 / ゲノム全領域関連解析 / 遺伝子 / 一塩基多型 / 糖尿病性腎症 / 高血圧性腎硬化症 / 末期腎不全 / 心血管疾患

Outline of Annual Research Achievements

平成26年度の研究成果
欧米のゲノム全領域関連解析のメタアナリシスで同定された冠動脈疾患感受性遺伝子の一塩基多型群（SNPs）のうち、日本人でマイナーアリル頻度が0.015以上である29種類のSNPsと慢性腎臓病との関連について、慢性腎臓病1588例および対照659例において解析した。その結果、IL6R遺伝子のrs4845625（T→C）多型（P = 0.0008; odds ratio, 1.49）が慢性腎臓病と有意に関連した。IL6R遺伝子のrs4845625多型は血清クレアチニン濃度、eGFRとも有意に関連した。これらの結果から、IL6R遺伝子のrs4845625多型は日本人の慢性腎臓病感受性遺伝子であることが示唆された。

研究期間全体の研究成果
平成24～26年度の研究で同定した慢性腎臓病感受性遺伝子のSNPs加え、年齢・性別・肥満・喫煙・高血圧・糖尿病・脂質異常症を包括した慢性腎臓病の個別化予防システムのプロトタイプモデルを開発した。本システムでは、慢性腎臓病を発症するリスク、ならびに発症リスクにおける各SNPおよびその他の因子の寄与率が算出できる。本システムにより、慢性腎臓病に関する個人の発症リスクを予測し、遺伝因子以外の治療・改善可能な因子に関して「生活習慣の改善あるいは治療によりどの危険因子を改善・除去すればどれだけ発症リスクが減少するか」についても予測する。健診センターや病院、クリニックにおいて、希望者に対し発症リスクを予測し、結果について医師あるいは遺伝カウンセラーによるカウンセリングを行う。リスクが高い場合には生活習慣の改善や、危険因子の早期治療を行うことにより慢性腎臓病の予防を積極的に推進する。特に慢性腎臓病の家族歴がある人々への適用が有効である。本システムを用いて慢性腎臓病の個別化予防を行ない、とりわけ心筋梗塞・脳梗塞・末期腎不全などの重篤な疾患を予防することにより、中高年者の健康維持・健康長寿・生活の質の向上・ねたきり防止への貢献が期待できる。

Research Products

• [Journal Article] Association of a polymorphism of the interleukin 6 receptor gene with chronic kidney disease in Japanese individuals (2015)
  • Author(s): Horibe H, Fujimaki T, Oguri M, Kato K, Matsuoka R, Abe S, Tokoro F, Arai M, Noda T, Watanabe S, Yamada Y
  • Journal Title: Nephrology Volume: 20 Pages: 273-278
  • DOI: 10.1111/nep.12381
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Association of polymorphisms of TOMM40 and SLC22A4 with ischemic stroke (2015)
  • Author(s): Yamase Y, Horibe H, Ueyama C, Fujimaki T, Oguri M, Kato K, Arai M, Watanabe S, Yamada Y
  • Journal Title: Biomed Rep Volume: in press Pages: in press
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Association of polymorphisms of FURIN and ZPR1 with metabolic syndrome (2015)
  • Author(s): Ueyama C, Horibe H, Yamase Y, Fujimaki T, Oguri M, Kato K, Arai M, Watanabe S, Murohara T, Yamada Y
  • Journal Title: Biomed Rep Volume: in press Pages: in press
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Association of genetic variants with dyslipidemia (2015)
  • Author(s): Abe S, Tokoro F, Matsuoka R, Arai M, Noda T, Watanabe S, Horibe H, Fujimaki T, Oguri M, Kato K, Minatoguchi S, Yamada Y
  • Journal Title: Mol Med Rep Volume: in press Pages: in press
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Association of genetic variants with dyslipidemia and chronic kidney disease in a longitudinal population-based genetic epidemiological study (2015)
  • Author(s): Yamada Y, Matsui K, Takeuchi I, Fujimaki T
  • Journal Title: Int J Mol Med Volume: 35 Pages: 1290-1300
  • DOI: 10.3892/ijmm.2015.2152
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Association of genetic variants with coronary artery disease and ischemic stroke in a longitudinal population-based genetic epidemiological study (2015)
  • Author(s): Yamada Y, Matsui K, Takeuchi I, Fujimaki T
  • Journal Title: Biomed Rep Volume: 3 Pages: 413-419
  • DOI: 10.3892/br.2015.440
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Association of genetic variants of the alpha-kinase 1 gene with type 2 diabetes mellitus in a longitudinal population-based genetic epidemiological study (2015)
  • Author(s): Yamada Y, Matsui K, Takeuchi I, Oguri M, Fujimaki T
  • Journal Title: Biomed Rep Volume: 3 Pages: 347-354
  • DOI: 10.3892/br.2015.439
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Association of genetic variants with hypertension in a longitudinal population-based genetic epidemiological study (2015)
  • Author(s): Yamada Y, Matsui K, Takeuchi I, Oguri M, Fujimaki T
  • Journal Title: Int J Mol Med Volume: 35 Pages: 1189-1198
  • DOI: 10.3892/ijmm.2015.2151
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Association of six genetic variants with myocardial infarction (2015)
  • Author(s): Matsuoka R, Abe S, Tokoro F, Arai M, Noda T, Watanabe S, Horibe H, Fujimaki T, Oguri M, Kato K, Minatoguchi S, Yamada Y
  • Journal Title: Int J Mol Med Volume: 35 Pages: 1451-1459
  • DOI: 10.3892/ijmm.2015.2115
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Association of a genetic variant of the ZPR1 zinc finger gene with type 2 diabetes mellitus (2015)
  • Author(s): Tokoro F, Matsuoka R, Abe S, Arai M, Noda T, Watanabe S, Horibe H, Fujimaki T, Oguri M, Kato K, Minatoguchi S, Yamada Y
  • Journal Title: Biomed Rep Volume: 3 Pages: 88-92
  • DOI: 10.3892/br.2014.379
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Association of a transcription factor 21 gene polymorphism with hypertension (2015)
  • Author(s): Fujimaki T, Oguri M, Horibe H, Kato K, Matsuoka R, Abe S, Tokoro F, Arai M, Noda T, Watanabe S, Yamada Y
  • Journal Title: Biomed Rep Volume: 3 Pages: 118-122
  • DOI: 10.3892/br.2014.371
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Identification of hypo- and hypermethylated genes related to atherosclerosis by a genome-wide analysis of DNA methylation (2015)
  • Author(s): Yamada Y, Nishida T, Horibe H, Oguri M, Kato K, Sawabe M
  • Journal Title: Int J Mol Med Volume: 33 Pages: 1355-1363
  • DOI: 10.3892/ijmm.2014.1692
  • Peer Reviewed / Acknowledgement Compliant
• [Presentation] Identification of hypo- and hypermethylated genes related to atherosclerosis by a genome-wide analysis of DNA methylation (2014)
  • Author(s): Oguri M, Yamada Y
  • Organizer: 19th World Congress on Advances in Oncology and 17th International Symposium on Molecular Medicine
  • Place of Presentation: Athens, Greece
  • Year and Date: 2014-10-09 – 2014-10-11
  • Invited
• [Presentation] Identification of chromosome 3q28 and ALPK1 as susceptibility loci for chronic kidney disease in Japanese individuals (2014)
  • Author(s): Yamada Y, Oguri M
  • Organizer: 19th World Congress on Advances in Oncology and 17th International Symposium on Molecular Medicine
  • Place of Presentation: Athens, Greece
  • Year and Date: 2014-10-09 – 2014-10-11
  • Invited
• [Presentation] Association of a polymorphism of the transcription factor 21 gene (TCF21) with hypertension in Japanese individuals (2014)
  • Author(s): Fujimaki T, Oguri M, Kato K, Matsuoka R, Abe S, Tokoro F, Arai M, Noda T, Watanabe S, Yamada Y
  • Organizer: European Society of Cardiology Congress 2014
  • Place of Presentation: Barcelona, Spain
  • Year and Date: 2014-08-30 – 2014-09-03
• [Presentation] Association of genetic variants of the alpha-kinase 1 gene (ALPK1) with type 2 diabetes mellitus in community-dwelling Japanese individuals (2014)
  • Author(s): Fujimaki T, Oguri M, Horibe H, Kato K, Yamada Y
  • Organizer: European Society of Cardiology Congress 2014
  • Place of Presentation: Barcelona, Spain
  • Year and Date: 2014-08-30 – 2014-09-03
• [Presentation] Association of genetic variants of the alpha-kinase 1 gene (ALPK1) with myocardial infarction in community-dwelling Japanese individuals (2014)
  • Author(s): Fujimaki T, Oguri M, Horibe H, Kato K, Yamada Y
  • Organizer: European Society of Cardiology Congress 2014
  • Place of Presentation: Barcelona, Spain
  • Year and Date: 2014-08-30 – 2014-09-03
• [Presentation] Association of genetic variants of the phosphatase and actin regulator 1 gene (PHACTR1) and the CDKN2B antisense RNA 1 (CDKN2BAS1) with coronary heart disease in Japanese individuals (2014)
  • Author(s): Matsuoka R, Abe S, Tokoro F, Arai M, Noda T, Watanabe S, Fujimaki T, Oguri M, Kato K, Yamada Y
  • Organizer: European Society of Cardiology Congress 2014
  • Place of Presentation: Barcelona, Spain
  • Year and Date: 2014-08-30 – 2014-09-03
• [Presentation] Association of a polymorphism of the zinc finger protein 259 gene (ZNF259) with dislipidemia in Japanese individuals (2014)
  • Author(s): Abe S, Tokoro F, Matsuoka R, Arai M, Noda T, Watanabe S, Fujimaki T, Oguri M, Kato K, Yamada Y
  • Organizer: European Society of Cardiology Congress 2014
  • Place of Presentation: Barcelona, Spain
  • Year and Date: 2014-08-30 – 2014-09-03
• [Presentation] Association of a genetic variant of the zinc finger protein 259 gene (ZNF259) with type 2 diabetes mellitus in Japanese individuals (2014)
  • Author(s): Tokoro F, Matsuoka R, Abe S, Arai M, Noda T, Watanabe S, Fujimaki T, Oguri M, Kato K, Yamada Y
  • Organizer: European Society of Cardiology Congress 2014
  • Place of Presentation: Barcelona, Spain
  • Year and Date: 2014-08-30 – 2014-09-03
• [Remarks] 生命科学研究支援センターヒト機能ゲノミクス部門
  • URL: http://www.lsrc.mie-u.ac.jp/human/