Epigenome alternations of sarcomeric genes in human dilated cardiomyopathy

• Project/Area Number: 19K08547
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 53020:Cardiology-related
• Research Institution: Iwate Medical University
• Principal Investigator: Satoh Mamoru 岩手医科大学, 医歯薬総合研究所, 客員教授 (90305996)
• Co-Investigator(Kenkyū-buntansha): 大桃 秀樹 岩手医科大学, 医歯薬総合研究所, 講師 (90453406)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Project Status: Completed (Fiscal Year 2021)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2021: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2020: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
• Keywords: 拡張型心筋症 / サルコメア遺伝子 / DNAメチル化 / エピジェネティクス異常 / サルコメア蛋白遺伝子群 / DNA メチル化 / microRNA / エピゲノム / マイクロRNA

Outline of Research at the Start

DCM群および対照群から採取した心筋生検組織を対象とし、サルコメア蛋白遺伝子群(β-ミ オシン重鎖1遺伝子、トロポニン T遺伝子、トロポニン I遺伝子およびα-トロポミオシン遺 伝子)をコードするCpGサイトのDNAメチル化解析を行い、DCMに特異的なDNAメチル化部位を 同定する。
上記のサルコメア蛋白遺伝子のトランスクプトーム制御するmicroRNA発現異常について解析を行い、DNAメチル化との関連解析を行いDCMの発症のメカニズムを探求する。
病態の進行および生命予後に関連するエピジェネティクス制御異常を探索する。

Outline of Final Research Achievements

This study has investigated epigenome alternations of sarcomeric genes in human dilated cardiomyopathy (DCM). This study included 50 patients with DCM and 50 control subjects. Genome DNA was taken from endomyocardial biopsy samples obtained from patients wtih DCM and controls. Ten DNA methylation sites of sarcomeric genes were analyzed using PyroMark system. There was no significant differences in DNA methylation between patients wtih DCM and controls. This study has established the methodology of epigenome alternations of sarcomeric genes in human DCM.

Academic Significance and Societal Importance of the Research Achievements

本研究では、孤発性拡張型心筋症(DCM)でのサルコメア蛋白遺伝子異常、特に、DNAメチル化解析に着目して検討した。10箇所の代表的なサルコメア蛋白遺伝子のDNAメチル化部位について解析したが、DCMに特異的なDNAメチル化部位を同定には至らなかった。しかし、本研究の学術的意義して心筋生検組織を用いたDNAメチル化解析の方法論を確立が挙げられる。

Research Products

• [Journal Article] Association between Social Isolation and Total Mortality after the Great East Japan Earthquake in Iwate Prefecture: Findings from the TMM CommCohort Study (2022)
  • Author(s): Kotozaki Y, Tanno K, Sakata K, Otsuka K, Sasaki R, Takanashi N, Satoh M, Shimizu A, Sasaki M.
  • Journal Title: Int J Environ Res Public Health. Volume: 19 Issue: 7 Pages: 4343-4353
  • DOI: 10.3390/ijerph19074343
  • Peer Reviewed / Open Access
• [Journal Article] Study Profile of the Tohoku Medical Megabank Community-Based Cohort Study (2021)
  • Author(s): Hozawa A, Tanno K, Nakaya N, Nakamura T, Tsuchiya N, Hirata T, Narita A, Kogure M, Nochioka K, Sasaki R, Takanashi N, Otsuka K, Sakata K, Kuriyama S, Kikuya M, 13名略, Kobayashi T, 53名略, Yamamoto M.
  • Journal Title: Journal of Epidemiology Volume: 31 Issue: 1 Pages: 65-76
  • DOI: 10.2188/jea.JE20190271
  • NAID: 130007966030
  • ISSN: 0917-5040, 1349-9092
  • Year and Date: 2021-01-05
  • Peer Reviewed / Open Access
• [Journal Article] Association between the social isolation and depressive symptoms after the great East Japan earthquake: findings from the baseline survey of the TMM CommCohort study (2021)
  • Author(s): Kotozaki Y, Tanno K, Sakata K, Takusari E, Otsuka K, Tomita H, Sasaki R, Takanashi N, Mikami T, Hozawa A, Nakaya N, Tsuchiya N, Nakamura T, Narita A, Taki Y, Shimizu A, Hitomi J, Satoh M, Sasaki M.
  • Journal Title: BMC Public Health. Volume: 21 Issue: 1 Pages: 925-935
  • DOI: 10.1186/s12889-021-10896-5
  • Peer Reviewed / Open Access
• [Journal Article] dbTMM: an integrated database of large-scale cohort, genome and clinical data for the Tohoku Medical Megabank Project (2021)
  • Author(s): Ogishima Soichi et al.
  • Journal Title: Human Genome Variation Volume: 8 Issue: 1 Pages: 44-51
  • DOI: 10.1038/s41439-021-00175-5
  • Peer Reviewed / Open Access
• [Journal Article] Plasma Xanthine Oxidoreductase Activity Is Associated with a High Risk of Cardiovascular Disease in a General Japanese Population (2021)
  • Author(s): Kotozaki Y, Satoh M, Tanno K, Ohmomo H, Otomo R, Tanaka F, Nasu T, Taguchi S, Kikuchi H, Kobayashi T, Shimizu A, Sakata K, Hitomi J, Sobue K, Sasaki M.
  • Journal Title: Int J Environ Res Public Health. Volume: 18 Issue: 4 Pages: 1894-1894
  • DOI: 10.3390/ijerph18041894
  • Peer Reviewed / Open Access
• [Journal Article] The Value of a Cystatin C-based Estimated Glomerular Filtration Rate for Cardiovascular Assessment in a General Japanese Population: Results From the Iwate Tohoku Medical Megabank Project (2020)
  • Author(s): Osaki T, Satoh M, Tanaka F, Tanno K, Takahashi Y, Nasu T, Sakata K, Morino Y, Sobue K, Sasaki M.
  • Journal Title: Journal of Epidemiology Volume: 30 Issue: 6 Pages: 260-267
  • DOI: 10.2188/jea.JE20180274
  • NAID: 130007852130
  • ISSN: 0917-5040, 1349-9092
  • Year and Date: 2020-06-05
  • Peer Reviewed / Open Access
• [Journal Article] Transethnic Meta-Analysis of Genome-Wide Association Studies Identifies Three New Loci and Characterizes Population-Specific Differences for Coronary Artery Disease (2020)
  • Author(s): Matsunaga Hiroshi, ... Ogishima Soichi et al.
  • Journal Title: Circulation: Genomic and Precision Medicine Volume: 13 Issue: 3
  • DOI: 10.1161/circgen.119.002670
  • Peer Reviewed / Open Access
• [Journal Article] A genome-wide association study for highly sensitive cardiac troponin T levels identified a novel genetic variation near a RBAK-ZNF890P locus in the Japanese general population (2020)
  • Author(s): Nasu T, Satoh M, Hachiya T, Sutoh Y, Ohmomo H, Hitomi S, Taguchi S, Kikuchi H, Kobayashi T, Takahashi Y, Osaki T, Morino Y, Sobue K, Shimizu A, Sasaki M.
  • Journal Title: Int J Cardiol. Volume: 329 Pages: 186-191
  • DOI: 10.1016/j.ijcard.2020.12.019
  • Peer Reviewed
• [Journal Article] Epigenome-Wide Association Study Identifies a Novel DNA Methylation in Patients With Severe Aortic Valve Stenosis. (2020)
  • Author(s): Nasu T, Satoh M, Ohmomo H, Shiwa Y, Komaki S, Ono K, Shimizu A, Taguchi S, Takahashi Y, Osaki T, Morino Y, Sobue K, Sasaki M.
  • Journal Title: Circ Genom Precis Med. Volume: 13 Issue: 1
  • DOI: 10.1161/circgen.119.002649
  • Peer Reviewed
• [Journal Article] Association between high-sensitivity cardiac troponin T and future cardiovascular incidence in a general Japanese population: results from the Tohoku medical megabank project. (2019)
  • Author(s): Takahashi Y, Satoh M, Ohmomo H, Tanaka F, Osaki T, Tanno K, Nasu T, Sakata K, Morino Y, Sobue K, Sasaki M
  • Journal Title: Biomarkers. Volume: 24 Issue: 6 Pages: 566-573
  • DOI: 10.1080/1354750x.2019.1606278
  • Peer Reviewed