Drug induced lung disease by MUC4 gene

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K17643
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 53030:Respiratory medicine-related
• Research Institution: Jichi Medical University
• Principal Investigator: Shiihara Jun 自治医科大学, 医学部, 助教 (20737241)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: 薬剤性間質性肺炎 / EGFR-TKI / MUC4

Outline of Final Research Achievements

We performed this study to clarify the genetic factor in Japanese which cause the fatal interstitial lung disease caused by EGFR-TKI : epidermal growth factor receptor tyrosine kinase inhibitor.
We had studied the exon2 of MUC4 gene. The genetic polymorphism in exon2 of MUC4 gene had been thought to cause the interstitial lung disease, but found to be not in the end.
Next we identify the whole sequence of exon2 of MUC4. We performed the case control study between case group and control group. We found the cos5 allele in the case group, but couldn't prove it to be the cause of the interstitial lung disease.

Free Research Field

肺癌、間質性肺炎

Academic Significance and Societal Importance of the Research Achievements

日本人において致死的な薬剤性間質性肺炎の原因となる遺伝子変異を同定する目的で研究を開始した。これまでの研究でMUC4遺伝子がその原因遺伝子であると考えたため、本研究では、MUC4のexon2における疾患関連遺伝子多型を同定することに注力した。当初認められていた3塩基多型や塩基配列同定により判明したcos5アレルも、症例数や浸透率が原因か、有意とは言えない結果になった。しかしMUC4が薬剤性間質性肺炎に関連している可能性は高いことはこれら研究からも明らかであり、引き続きの研究で日本人特異的遺伝子的特徴の解明につながることが期待される