Analysis of disease-pathways and molecular targets by disease-susceptibility genes in primary biliary cholangitis

2016 Fiscal Year Final Research Report

• Project/Area Number: 26293181
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: Gastroenterology
• Research Institution: Department of Clinical Research, National Hospital Organization Nagasaki Medical Center
• Principal Investigator: Nakamura Minoru 独立行政法人国立病院機構(長崎医療センター臨床研究センター), 臨床研究センター, 客員研究員 (40217906)
• Co-Investigator(Kenkyū-buntansha): 川嶋 実苗 国立研究開発法人科学技術振興機構, バイオサイエンスデーターベースセンター, 研究員 (00396706) ; 人見 祐基 東京大学, 大学院医学系研究科(医学部), 助教 (10525819) ; 下田 慎治 九州大学, 大学病院, 講師 (30279319) ; 西田 奈央 国立研究開発法人国立国際医療研究センター, その他部局等, その他 (50456109) ; 安波 道郎 長崎大学, 熱帯医学研究所, 教授 (80244127)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Keywords: 原発性胆汁性胆管炎 / ゲノムワイド関連解析 / 疾患感受性遺伝子 / 疾患発症経路 / 分子標的

Outline of Final Research Achievements

We performed GWAS in additional 1,923 Japanese individuals (894 PBC cases and 1,029 healthy controls), and combined the results with the previous data (487 PBC cases and 476 healthy controls). This combined GWAS identified TNFSF15, POU2AF1, IL7R, IKZF3 as PBC-susceptibility loci at a GWAS-significant level (P<5xE-8) , and identified PRKCB as a novel susceptibility locus by a subsequent replication study in an independent set of 7,024 Japanese individuals (512 PBC cases and 6,512 healthy controls). Furthermore, primary functional variants of TNFSF15, PRKCB, IKZF3 loci was identified by genotype imputation using a phased panel of 1,070 Japanese individuals from a prospective, general population cohort study and subsequent in vitro functional analyses. These results may lead to improved understanding of the disease pathways involved in PBC, forming a basis for prevention of PBC and development of novel therapeutics.

Free Research Field

肝臓病学