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

2023 Fiscal Year Final Research Report

• Project/Area Number: 20K17812
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 55050:Anesthesiology-related
• Research Institution: Hiroshima University
• Principal Investigator: Noda Yuko 広島大学, 病院(医), 助教 (00790065)
• Project Period (FY): 2021-11-01 – 2024-03-31
• 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

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.

Free Research Field

麻酔蘇生学

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．