Searching for the genetic factors predisposing to PBC

2017 Fiscal Year Final Research Report

• Project/Area Number: 15K06908
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Medical genome science
• Research Institution: The University of Tokyo
• Principal Investigator: KAWASHIMA Minae 東京大学, 大学院医学系研究科(医学部), 客員研究員 (00396706)
• Co-Investigator(Renkei-kenkyūsha): NAKAMURA Minoru 長崎医療センター, 臨床研究センター, 客員研究員 (40217906) ; TOKUNAGA Katsushi 東京大学, 大学院医学系研究科, 教授 (40163977) ; NISHIDA Nao 国立国際医療研究センター, 肝炎・免疫研究センター, 上級研究員 (50456109)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Keywords: PBC / 遺伝要因探索 / ゲノムワイド関連解析 / replication study / 層別化解析 / 国際共同研究

Outline of Final Research Achievements

Primary biliary cholangitis (PBC) is a chronic and progressive cholestatic liver disease, presumably caused by autoimmune reactions against biliary epithelial cells, leading to liver cirrhosis and hepatic failure. The incidence and prevalence of PBC range from 0.33 to 5.8 and from 2 to 40 per 100,000 inhabitants, respectively, in different geographical areas. Additionally, it is much more common in women, with a sex ratio of at least 7:1 female to male. The high concordance rate in monozygotic twins compared to dizygotic twins and familial clustering of PBC patients indicates the involvement of strong genetic factors in the development of PBC. For the identification of susceptibility genetic factors for pathology, progression, and pathology of PBC, a genome-wide association study (GWAS) and classification analyses were performed in a large number of Japanese individuals (1381 PBC cases and 1505 healthy controls). Functional analyses in vivo and in silico were also performed.

Free Research Field

Human Genetics