Exploration of disease associated pathway and lncRNA in connective tissue diseases by a comprehensive expression analysis

2018 Fiscal Year Final Research Report

• Project/Area Number: 16K09886
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Collagenous pathology/Allergology
• Research Institution: University of Tsukuba
• Principal Investigator: Kawasaki Aya 筑波大学, 医学医療系, 助教 (30532816)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: ANCA関連血管炎 / long non-coding RNA / 疾患感受性遺伝子

Outline of Final Research Achievements

It is likely that multiple genetic factors contribute to the pathogenesis of ANCA-associated vasculitis (AAV) and systemic lupus erythematosus (SLE). However, actual genetic variants that play a role in the pathogenesis have not fully determined. In this study, we tried to find new susceptibility genes by focusing on single nucleotide variant (SNV) which may potentially affect gene expression. Initially, we searched for disease-associated pathway genes and long non-coding RNA (lncRNA) by a comprehensive expression analysis. This analysis suggested that interferon pathway and lncRNA are substantially involved in the pathogenesis of AAV and SLE. Subsequent association study targeted to SNVs of the differentially expressed lncRNAs in the diseases identified ATP6V0E2-AS1 as a potential susceptibility gene to AAV.

Free Research Field

ゲノム医科学、膠原病学

Academic Significance and Societal Importance of the Research Achievements

難治性疾患であるANCA関連血管炎(AAV)は、罹患率の低さから他の膠原病と比較しても疾患発症に寄与する遺伝要因の解明は遅れている。本研究で見出されたlong non-coding RNAであるATP6V0E2-AS1は、AAVにおいて発現が減少しており、さらに転写調節領域に位置するバリアントがAAVの疾患感受性と関連することから、疾患発症や病態形成に寄与する可能性が高く、ATP6V0E2-AS1をターゲットとした治療薬の開発が期待できる。