2023 Fiscal Year Final Research Report
GWAS and post-GWAS on genes associated with occurrence of ANCA-associated vasculitis and comorbidity of interstitial lung diseases.
| Project/Area Number |
21K08435
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Review Section |
Basic Section 54020:Connective tissue disease and allergy-related
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| Research Institution | University of Tsukuba |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
針谷 正祥 東京女子医科大学, 医学部, 教授 (20238207)
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| Project Period (FY) |
2021-04-01 – 2024-03-31
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| Keywords | ANCA関連血管炎 / 疾患感受性遺伝子 / 再燃 / HLA / 間質性肺疾患 / ゲノムワイド関連研究 / SERPINA1 |
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| Outline of Final Research Achievements |
This study investigated genetic variants associated with susceptibility and risk of relapse of ANCA-associated vasculitis (AAV) in the Japanese population, as well as those associated with development of interstitial lung disease (AAV-ILD). Using a genomewide association study, 22 variants associated with AAV-ILD were detected. HLA-DRB1*09:01-DQA1*03:02-DQB1*03:03 haplotype was associated with both susceptibility and risk of relapse of MPO-ANCA positive AAV, and HLA-DRB1 position 13Ser was associated with lower risk of relapse. Eosiniphilic granulomatosis with polyangiitis (EGPA) was associated with HLA-DRB1*07:01 and *09:01. Finally, although SERPINA1 Z and S alleles, associated with granulomatosis with polyangiitis (GPA) and PR3-ANCA positive AAV in the populations of European ancestry, were not dected in the Japanese subjects, SERPINA1 alleles previously unreported to be associated with AAV were found to be associated with GPA/PR3-AAV in the Japanese population.
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| Free Research Field |
膠原病学、ゲノム医科学
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| Academic Significance and Societal Importance of the Research Achievements |
東アジア集団におけるAAVの疫学はヨーロッパ系集団と大きく異なる。本研究から、日本人AAVの大部分を占めるMPO-ANCA陽性血管炎の再燃リスクに関連するHLAハプロタイプが明らかになったことは、寛解後の維持療法の個別化に応用しうる知見である。また、これまで日本人集団では疾患感受性に関連しないと考えられてきたSERPINA1に、ヨーロッパ系集団とは異なるリスクアリルが検出されたことは、学術的意義の高い新知見である。さらに、ILD合併関連遺伝子のゲノムワイド関連研究により候補領域が多数見出されたことは、難治性病態であるILDに対する分子標的の発見に結びつくと期待される。
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