Investigation of the mechanism by which abnormal metabolism of homocysteine is involved in the development of COPD.

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K16107
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 53030:Respiratory medicine-related
• Research Institution: Yamagata University
• Principal Investigator: Nakano Hiroshi 山形大学, 医学部, 医員 (80637629)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: 慢性閉塞性肺疾患 / 喫煙 / 呼吸機能 / 肺気腫 / ホモシステイン / 小胞体ストレス / MTHFR / アポトーシス

Outline of Final Research Achievements

Epidemiological studies analyzed the association between single nucleotide polymorphisms involving methylenetetrahydrofolate reductase (MTHFR) and changes in respiratory function test findings over time using data from the Takahata study. In rs4846049, rs1476413, rs1994798, and rs4846052, study participants who were current smokers and major homozygotes had a significantly higher rate of decline in one second volume over time compared to study participants who were minor homozygotes or heterozygotes.In the basic study, MTHFR gene knockout mice were generated using CRISPR-Cas9. They were successfully bred and started smoking exposure.

Free Research Field

呼吸器病学

Academic Significance and Societal Importance of the Research Achievements

世界的な死因となっている慢性閉塞性肺疾患の病因として喫煙感受性が存在する可能性が報告されているが、本研究結果はMTHFR遺伝子変異がその一因である可能性を示唆し、慢性閉塞性肺疾患の発症機序解明や治療と予防方法の開発の一助となり得る。