Impact of epigenetic changes on complication of chronic kidney disease

• Project/Area Number: 16K08975
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Laboratory medicine
• Research Institution: Showa University
• Principal Investigator: Honda Hirokazu 昭和大学, 医学部, 教授 (70297000)
• Co-Investigator(Kenkyū-buntansha): 小林 靖奈 新潟薬科大学, 薬学部, 教授 (20276611)
• Project Period (FY): 2016-04-01 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2019: ¥390,000 (Direct Cost: ¥300,000、Indirect Cost: ¥90,000); Fiscal Year 2018: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000); Fiscal Year 2017: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000); Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: エピジェネティクス / 慢性腎臓病 / 心血管病 / 栄養障害 / 後成的遺伝子変性 / 抗加齢因子 / 透析 / 後天的DNA変性 / 血液透析 / 腎機能 / klotho遺伝子 / DNAメチル化 / 後天的遺伝子変性 / 長寿遺伝子 / 慢性炎症 / 栄養

Outline of Final Research Achievements

The aim of this study was to assess impact of epigenetic changes on complication, cardiovascular disease (CVD) and malnutrition, of chronic kidney disease. Prevalence of epigenetic changes of klotho and sirtuin 1 promoter gene methylation were increased in both CKD stage 4-5 and hemodialysis patients and tended to be increased in non-CKD patients with CVD. In dialysis patients, klotho promoter gene methylation was associated with high prevalence of CVD history and low score of geriatric nutritional risk index.

Academic Significance and Societal Importance of the Research Achievements

慢性腎臓病（CKD)は慢性炎症・酸化ストレスを呈することが多く、心血管病や栄養障害の合併頻度が高い。本研究では慢性炎症・酸化ストレス環境での抗加齢因子の後成的遺伝子変化に焦点を当て、心血管病や栄養障害との関係を探索することである。本研究成果からCKD患者では抗加齢因子の後成的変化が心血管病や栄養障害の発症と関係する可能性が考えら、それらの合併症に対するDNAメチル化診断が可能となる。また、DNAの後成的変化は可逆的である為、新規治療戦略へ展開が可能となる。その結果、予防医療や在宅医療の推進などの医療費の削減につながる研究成果と考える。

Research Products

• [Journal Article] N-Terminal Pro-B-Type Natriuretic Peptide as a Biomarker for Loss of Muscle Mass in Prevalent Hemodialysis Patients. (2016)
  • Author(s): Ikeda M, Honda H, Takahashi K, Shishido K, Shibata T.
  • Journal Title: PLoS One. Volume: 11 Issue: 11 Pages: e0166804-e0166804
  • DOI: 10.1371/journal.pone.0166804
  • Peer Reviewed / Open Access
• [Presentation] DNA methylation of Klotho promotor gene is associated with prevalence of cardiovascular disease in patients under hemodialysis (2018)
  • Author(s): Hirokazu Honda, Yasuna Kobayashi, Seiki Aruga, Daijiro Uetake, Takanori Shibata
  • Organizer: ERA-EDTA
• [Presentation] DNA methylation of Klotho promotor gene is associated with cardiovascular disease and malnutrition in patients under hemodialysis (2018)
  • Author(s): Hirokazu Honda, Yasuna Kobayashi, Seiki Aruga, Daijiro Uetake, Takanori Shibata
  • Organizer: 米国腎臓学会
• [Presentation] 血液透析患者における後天的Klotho遺伝子変性について (2018)
  • Author(s): 本田浩一、小林靖奈、有賀誠記、上竹大二郎、柴田孝則
  • Organizer: 日本腎臓学会