Pharmacogenomics study of anti-tuberculosis drugs in the Asian population
| Project/Area Number |
24406010
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Partial Multi-year Fund |
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| Section | 海外学術 |
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| Research Field |
Human genetics
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| Research Institution | The University of Tokyo |
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Principal Investigator |
TOKUNAGA Katsushi 東京大学, 医学(系)研究科(研究院), 教授 (40163977)
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| 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)
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| Research Collaborator |
OMAE Yousuke
NAKAUCHI Ayaka
MAHASIRIMONGKOL Surakameth
WATTANAPOKAYAKIT Sukanya
YULIWULANDARI Rika
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| Project Period (FY) |
2012-04-01 – 2015-03-31
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| Project Status |
Completed (Fiscal Year 2014)
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| Budget Amount *help |
¥17,290,000 (Direct Cost: ¥13,300,000、Indirect Cost: ¥3,990,000)
Fiscal Year 2014: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2013: ¥5,720,000 (Direct Cost: ¥4,400,000、Indirect Cost: ¥1,320,000)
Fiscal Year 2012: ¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
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| 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 / アジア系集団 / 人類遺伝学 / 薬剤副作用 / 薬剤応答性 / 国際情報交換 / 日本 / 遺伝子 / 国際研究者交流 / 日本:タイ |
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| 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.
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Report
(4 results)
Research Products
(22 results)
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[Journal Article] Diagnostic value of blood gene expression signatures in active tuberculosis in Thais: a pilot study2015
Author(s)
Satproedprai N, Wichukchinda N, Suphankong S, Inunchot W, Kuntima T, Kumpeerasart S, Wattanapokayakit S, Nedsuwan S, Yanai H, Higuchi K, Harada N, Mahasirimongkol S
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Journal Title
Genes Immun
Volume: 16
Issue: 4
Pages: 1-8
DOI
Related Report
Peer Reviewed
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[Journal Article] Genome-wide association studies of tuberculosis in Asians2012
Author(s)
Mahasirimongkol S, Yanai H, Mushiroda T, Promphittayarat W, Wattanapokayakit S, Promjai J, Yuliwulandari R, Wichukchinda N, Yowang A, Yamada N, Kantipong P, Takahashi A, Kubo M, Sawanpanyalert P, Kamatani N, Nakamura Y, Tokunaga K
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Journal Title
Journal of Human Genetics
Volume: 57巻(6)
Issue: 6
Pages: 363-367
DOI
Related Report
Peer Reviewed
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[Presentation] Association of NAT2 polymorphisms with anti-tuberculosis drug-induced liver injury in Thai patients2014
Author(s)
④Wattanapokayakit S, Mushiroda T, Yanai H, Wichukchinda N, Inunchot W, Chuchottawon C, Nedsuwan S, Denjanta S, Kantima T, Mahasirimongkol S, Tokunaga K
Organizer
日本人類遺伝学会第59回大会
Place of Presentation
タワーホール船堀
Year and Date
2014-11-19 – 2014-11-22
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[Presentation] Lineages-based Association Analysis in tuberculosis (Abstract No.864W)2013
Author(s)
Mahasirimongkol S, Smittipat N, Juthayothin T, Mushiroda T, Pokayawattanakit S, Wichukchinda N, Nedsuwan S, Dokladda K, Rukseree K, Billamas P, Palittapongarnpim P, Chaiyasirinroje B, Chaiprasert A, Yanai H, Tokunaga K
Organizer
the 63rd Annual Meeting of The American Society of Human Genetics(ASHG)
Place of Presentation
Boston Convention Center, Boston, MA, USA
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