Development of the personalized prevention system for chronic kidney disease

• Project/Area Number: 24590746
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Hygiene
• Research Institution: Mie University
• Principal Investigator: YAMADA Yoshiji 三重大学, 生命科学研究支援センター, 教授 (90333286)
• Co-Investigator(Kenkyū-buntansha): NISHIDA Tamotsu 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
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000); Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2013: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2012: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• 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 / 遺伝子多型 / 2型糖尿病 / 心筋梗塞

Outline of Final Research Achievements

We performed a genome-wide association study (GWAS) to identify genetic variants that confer susceptibility to chronic kidney disease (CKD). The initial GWAS for CKD was performed in 252 individuals with CKD and 249 controls. The replication studies were performed in 910 with CKD and 838 controls and in 190 with CKD and 1412 controls. The rs9846911 at 3q28 was significantly associated with CKD in all individuals and rs2074381 and rs2074380 of ALPK1 were associated with CKD in diabetic individuals. The 3q28 may be a susceptibility locus for CKD in Japanese individuals, and ALPK1 may be a susceptibility gene for CKD in such individuals with diabetes mellitus. A prototype model of the personalized prevention system for CKD was developed with conventional risk factors and the polymorphisms identified in the present study. This system predicts the future risk for CKD in each individual by calculating the prediction probability from the results of laboratory examination and genetic analysis.

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 Issue: 4 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
  • 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
  • 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
  • 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 Issue: 5 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 Issue: 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 Issue: 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 Issue: 5 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 Issue: 5 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 Issue: 1 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 Issue: 1 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 (2014)
  • Author(s): Yamada Y, Nishida T, Horibe H, Oguri M, Kato K, Sawabe M
  • Journal Title: Int J Mol Med Volume: 33 Issue: 5 Pages: 1355-63
  • DOI: 10.3892/ijmm.2014.1692
  • Peer Reviewed
• [Journal Article] Association of genetic variants of the alpha-kinase 1 gene with myocardial infarction in community-dwelling individuals (2014)
  • Author(s): Tetsuo Fujimaki, Hideki Horibe, Mitsutoshi Oguri, Kimihiko Kato, Yoshiji Yamada
  • Journal Title: Biomed Rep Volume: 2 Issue: 1 Pages: 127-131
  • DOI: 10.3892/br.2013.190
  • Peer Reviewed
• [Journal Article] Association between polymorphisms of the alpha-kinase 1 gene and type 2 diabetes mellitus in community-dwelling individuals (2013)
  • Author(s): Shigetaka Shimokata, Mitsutoshi Oguri, Tetsuo Fujimaki, Hideki Horibe, Kimihiko Kato, Yoshiji Yamada
  • Journal Title: Biomed Rep Volume: 1 Issue: 6 Pages: 940-944
  • DOI: 10.3892/br.2013.173
  • Peer Reviewed
• [Journal Article] Association of a polymorphism of BTN2A1 with chronic kidney disease in community-dwelling individuals (2013)
  • Author(s): Mitsutoshi Oguri, Tetsuo Fujimaki, Hideki Horibe, Kimihiko Kato, Sahoko Ichihara, Yoshiji Yamada
  • Journal Title: Biomed Rep Volume: 1 Issue: 6 Pages: 868-872
  • DOI: 10.3892/br.2013.176
  • Peer Reviewed
• [Journal Article] Identification of 3q28 and ALPK1 as susceptibility loci for chronic kidney disease in Japanese individuals by a genome-wide association study (2013)
  • Author(s): Yoshiji Yamada, Tamotsu Nishida, Sahoko Ichihara, Kimihiko Kato, Tetsuo Fujimaki, Mitsutoshi Oguri, Hideki Horibe, Sachiro Watanabe, Kei Satoh, Yukitoshi Aoyagi, Michio Fukuda, Motoji Sawabe
  • Journal Title: J Med Genet Volume: published online Pages: 1-9
  • Peer Reviewed
• [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
• [Presentation] Association of a polymorphism of BTN2A1 with chronic kidney disease in community-dwelling Japanese individuals (2014)
  • Author(s): Shigetake Shimokata, Mitsutoshi Oguri, Yoshihisa Shibata, Haruo Kamiya, Tetsuo Fujimaki, Hideki Horibe, Kiyoshi Yokoi, Kimihiko Kato, Toyoaki Murohara, Yoshiji Yamada
  • Organizer: 第78回日本循環器学会学術集会
  • Place of Presentation: 東京
• [Presentation] Association of genetic variants of ALPK1 with myocardial infarction in community-dwelling Japanese individuals (2014)
  • Author(s): Tetsuo Fujimaki, Hideki Horibe, Mitsutoshi Oguri, Kimihiko Kato, Nobuyuki Ohte, Yoshiji Yamada
  • Organizer: 第78回日本循環器学会学術集会
  • Place of Presentation: 東京
• [Presentation] Identification of chromosome 3q28 and ALPK1 as susceptibility loci for chronic kidney disease by a genome-wide association study (2014)
  • Author(s): Kimihiko Kato, Yoshiji Yamada, Sahoko Ichihara, Tetsuo Fujimaki, Mitsutoshi Oguri, Hideki Horibe, Kiyoshi Yokoi, Tetsuro Yoshida, Sachiro Watanabe, Toyoaki Murohara
  • Organizer: 第78回日本循環器学会学術集会
  • Place of Presentation: 東京
• [Presentation] Identification of chromosome 3q28 and ALPK1 as susceptibility loci for chronic kidney disease in Japanese individuals by a genome-wide association study (2013)
  • Author(s): Kimihiko Kato, Tetsuo Fujimaki, Mitsutoshi Oguri, Hideki Horibe, Sachiro Watanabe, Toyoaki Murohara, Motoji Sawabe, Tamotsu Nishida, Sahoko Ichihara, Yoshiji Yamada
  • Organizer: European Society of Cardiology Congress 2013
  • Place of Presentation: Amsterdam, Netherlands
• [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/
• [Patent(Industrial Property Rights)] 慢性腎臓病の遺伝的リスク検出法 (2013)
  • Inventor(s): 山田芳司、島田和典
  • Industrial Property Rights Holder: 三重大学、島田和典
  • Industrial Property Rights Type: 特許
  • Industrial Property Number: 2013-051824
  • Filing Date: 2013-02-28