• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to previous page

Exploring the association between heat/exertion intolerance and ryanodine receptor variants

Research Project

Project/Area Number 20K17812
Research Category

Grant-in-Aid for Early-Career Scientists

Allocation TypeMulti-year Fund
Review Section Basic Section 55050:Anesthesiology-related
Research InstitutionHiroshima University

Principal Investigator

Noda Yuko  広島大学, 病院(医), 助教 (00790065)

Project Period (FY) 2021-11-01 – 2024-03-31
Project Status Completed (Fiscal Year 2023)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2021: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
Fiscal Year 2020: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Keywords熱/労作不耐 / 労作性熱中症 / リアノジン受容体 / 悪性高熱症 / 遺伝学 / 遺伝子 / 次世代シークエンサー
Outline of Research at the Start

労作性熱中症(EHS)や運動誘発性横紋筋融解症などの熱/労作不耐を起因とする疾患の患者から悪性高熱症(MH)の原因遺伝子のひとつであるリアノジン受容体(RYR1)遺伝子の変異がみつかっていることから,熱/労作不耐とMHおよびRYR1遺伝子変異の関連性が示唆されているが,その詳細はまだ明らかになっていない.
本研究では,EHSおよび運動誘発性横紋筋融解症を発症した患者から採取した検体を用いて遺伝子解析を行い,検出されたRYR1遺伝子変異に関して機能解析を行うことで,RYR1遺伝子変異と熱/労作不耐の関連性を探求し,EHSや運動誘発性横紋筋融解症の発症リスクの評価診断に寄与することを目的とする.

Outline of Final Research Achievements

Heat and exertion intolerances, such as exertional heat stroke (EHS) and exercise-induced rhabdomyolysis, and malignant hyperthermia (MH), have different triggers but exhibit very similar clinical manifestations, suggesting a possible correlation.
Following approval by the Genetic Ethics Committee, blood samples were collected from patients who presented to the hospital with heat stroke. The purpose, significance, and use of the donated blood were explained in a written document, and written consent was obtained. DNA was extracted from the blood samples and analyzed for RYR1 gene variants; five RYR1 variants were identified in seven patients. Additionally, one gene variant for the capsaicin receptor TRPV1, a temperature-sensitive TRP channel, was found.

Academic Significance and Societal Importance of the Research Achievements

EHS患者からRYR1遺伝子変異がみつかっていることから,RYR1遺伝子変異がEHSの遺伝的要因の一つではないかと以前から考えられてきた.RYR1遺伝子変異は,熱/労作不耐に起因する可能性が高く,このことから,EHSや運動誘発性横紋筋融解症などの熱/労作不耐と悪性高熱症(MH)との相関が示唆されている.しかし,この相関に関する研究はまだ十分ではない.本研究では,熱中症患者からRYR1遺伝子変異を同定し,これにより,熱/労作不耐の原因とMHの原因遺伝子であるRYR1遺伝子変異との関連性をより明確にすることに少なからず寄与できた.

Report

(5 results)
  • 2023 Annual Research Report   Final Research Report ( PDF )
  • 2022 Research-status Report
  • 2021 Annual Research Report
  • 2020 Research-status Report
  • Research Products

    (1 results)

All 2023

All Journal Article (1 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 1 results,  Open Access: 1 results)

  • [Journal Article] Functional characterization of RYR1 variants identified in malignant hyperthermia susceptible individuals2023

    • Author(s)
      Noda Yuko、Miyoshi Hirotsugu、Benucci Sofia、Gonzalez Asensio、Bandschapp Oliver、Girard Thierry、Treves Susan、Zorzato Francesco
    • Journal Title

      Neuromuscular Disorders

      Volume: 33 Issue: 12 Pages: 951-963

    • DOI

      10.1016/j.nmd.2023.10.019

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research

URL: 

Published: 2020-04-28   Modified: 2025-01-30  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi