Pharmacogenomics study of anti-tuberculosis drugs in the Asian population

2014 Fiscal Year Final Research Report

• Project/Area Number: 24406010
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 海外学術
• Research Field: Human genetics
• Research Institution: The University of Tokyo
• Principal Investigator: TOKUNAGA Katsushi 東京大学, 医学(系)研究科(研究院), 教授 (40163977)
• Co-Investigator(Kenkyū-buntansha): MUSHIRODA Taisei 統合生命医科学研究センター, ファーマコゲノミクス研究グループ, グループデレクター (40392146) ; YANAI Hideki 東京大学, 大学院医学系研究科, 客員研究員 (60437845)
• Research Collaborator: OMAE Yousuke ; NAKAUCHI Ayaka ; MAHASIRIMONGKOL Surakameth ; WATTANAPOKAYAKIT Sukanya ; YULIWULANDARI Rika
• Project Period (FY): 2012-04-01 – 2015-03-31
• Keywords: 薬理遺伝学 / ゲノム医科学 / 結核 / 副作用 / 関連遺伝子 / 国際共同研究 / タイ / インドネシア

Outline of Final Research Achievements

We have been conducting International Collaborative TB Research in Asia. Anti-TB drug-induced liver injury (AT-DILI) is a main reason of treatment failure. A total of 138 Thai TB patients including 53 AT-DILI cases and 366 Japanese TB patients including 73 AT-DILI cases were enrolled. The odds ratios of N-acetyltransferase 2 (NAT2) slow acetylator (SA) status with AT-DILI were 8.80 (95% confidence interval (CI) 4.01-19.31, P-value = 1.53*10-8) in Thais and 4.32 (95%CI 1.93-9.66, p=5.56*10-5) in Japanese. Our results demonstrated that the acetylator status of NAT2 is an important determinant for AT-DILI in Asia. We performed first-phase genome-wide association study to search for the additional genetic factors. International meta-analysis and cost-effectiveness analysis may provide data to support the individualization of anti-TB treatment in Asian TB patients based on genotyping of the NAT2 and additional genes.

Free Research Field

人類遺伝学