HLA-omics-based pharmacogenomics for adverse drug reactions in genome cohort studies
| Project/Area Number |
17K19804
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| Research Category |
Grant-in-Aid for Challenging Research (Exploratory)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Society medicine, Nursing, and related fields
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| Research Institution | Kanazawa University |
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Principal Investigator |
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| Research Collaborator |
Tajima Atsushi 金沢大学, 医学系, 教授
Kannon Takayuki 金沢大学, 医学系, 特任助教
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| Project Period (FY) |
2017-06-30 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
Fiscal Year 2018: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
Fiscal Year 2017: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
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| Keywords | HLA / 薬剤副作用 / コホート研究 / ゲノム / 遺伝学 / 免疫学 |
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| Outline of Final Research Achievements |
The HLA region, a 3.6-Mb segment of the human genome at 6p21, has been associated with more than 100 different diseases, primarily autoimmune diseases. Furthermore, specific alleles of the HLA genes are strongly associated with hypersensitivities to specific drugs. For a better understanding of the adverse effects of drugs, the HLA gene and HLA haplotype structure should be extensively and unambiguously determined. Here we determined genotypes of 33 HLA genes for genome cohort samples and constructed HLA genotype database with various phenotypes including severe adverse effects of various drugs.
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| Academic Significance and Societal Importance of the Research Achievements |
HLA遺伝子と薬剤副作用の関連は非常に強いことは明らかであるが、なぜ免疫応答の入り口として自己と非自己を認識するHLAが薬剤副作用と関連するのか、その発症メカニズムはいまだ不明である。本研究により、薬剤副作用と特定のHLAアレルやハプロタイプとの関係が明確になれば、重篤な薬剤副作用を予測し、予防医学的診断システムとして実用化することが可能となる。さらに、薬剤代謝関連変異およびパスウェイとHLAの発現およびその制御を統合的に解析し、その発症メカニズムを明らかにすることも期待できる。
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Report
(3 results)
Research Products
(42 results)
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[Journal Article] Genetic and phenotypic landscape of the major histocompatibilty complex region in the Japanese population.2019
Author(s)
Hirata J, Hosomichi K, Sakaue S, Kanai M, Nakaoka H, Ishigaki K, Suzuki K, Akiyama M, Kishikawa T, Ogawa K, Masuda T, Yamamoto K, Hirata M, Matsuda K, Momozawa Y, Inoue I, Kubo M, Kamatani Y, Okada Y.
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Journal Title
Nat Genet
Volume: 51
Issue: 3
Pages: 470-480
DOI
Related Report
Peer Reviewed / Int'l Joint Research
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[Journal Article] Multiple common and rare variants of ABCG2 cause gout2017
Author(s)
Higashino Toshihide、Takada Tappei、Nakaoka Hirofumi、Toyoda Yu、Stiburkova Blanka、Miyata Hiroshi、Ikebuchi Yuki、Nakashima Hiroshi、Shimizu Seiko、Kawaguchi Makoto、Sakiyama Masayuki、Nakayama Akiyoshi、Akashi Airi、Tanahashi Yuki、Kawamura Yusuke、Nakamura Takahiro、Wakai Kenji、Hosomichi Kazuyoshi 他
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Journal Title
RMD Open
Volume: 3
Issue: 2
Pages: e000464-e000464
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Comprehensive genetic exploration of selective tooth agenesis of mandibular incisors by exome sequencing2017
Author(s)
Yamaguchi T, Hosomichi K, Yano K, Kim Y, Nakaoka H, Kimura R, Otsuka H, Nonaka N, Haga S, Takahashi M, Shirota T, Kikkawa Y, Yamada A, Kamijo R, Park SB, Nakamura M, Maki K, Inoue I
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Journal Title
Hum Genome Variation
Volume: 印刷中
Issue: 1
Pages: 17005-17005
DOI
NAID
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Identification of an HLA class I allele closely involved in the auto-antigen presentation in acquired aplastic anemia2017
Author(s)
Zaimoku Y, Takamatsu H, Hosomichi K, Ozawa T, Nakagawa N, Imi T, Maruyama H, Katagiri T, Kishi H, Tajima A, Muraguchi A, Kashiwase K, Nakao S
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Journal Title
Blood
Volume: 印刷中
Issue: 21
Pages: 2908-2916
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Rapid and cost-effective high-throughput sequencing for identification of germline mutations of BRCA1 and BRCA22017
Author(s)
Ahmadloo S, Nakaoka H, Hayano T, Hosomichi K, You H, Utsuno E, Sangai T, Nishimura M, Matsushita K, Hata A, Nomura F, Inoue I
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Journal Title
J Hum Genetics
Volume: 印刷中
Issue: 5
Pages: 561-567
DOI
NAID
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Presentation] 尿酸トランスポーター遺伝子ABCG2のレアバリアントはコモンバリアントと同様に痛風を引きおこす2018
Author(s)
松尾 洋孝, 東野 俊英, 高田 龍平, 中岡 博史, 豊田 優, 清水 聖子, 川口 真, 中山 昌喜, 青柳 有香, 中嶌 真由子, 河村 優輔, 中村 好宏, 若井 建志, 岡田 理恵子, 山本 健, 細道 一善, 市田 公美, 大山 博司, 井ノ上 逸朗, 四ノ宮 成祥
Organizer
日本人類遺伝学会第63回大会
Related Report
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[Presentation] 北海道船泊遺跡の高深度縄文人ゲノムから2018
Author(s)
神澤 秀明, ティモシー ジナム, 河合 洋介, 佐藤 丈寛, 細道 一善, 田嶋 敦, 安達 登, 松村 博文, キリル クリュコフ, 斎藤 成也, 篠田 謙一
Organizer
日本人類遺伝学会第63回大会
Related Report
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[Presentation] Loss-of-Function Mutations in HLA-Class I Alleles in Acquire Aplastic Anemia: Evidence for the Involvement of Limited Class I Alleles in the Auto-Antigen Presentation of Aplastic Anemia2018
Author(s)
Hiroki Mizumaki, Kazuyoshi Hosomichi, Tanabe Mikoto, Takeshi Yoroidaka, Tatsuya Imi, Yoshitaka Zaimoku, Kohei Hosokawa, Takamasa Katagiri, Hiroyuki Takamatsu, Tatsuhiko Ozawa, Fumihiro Azuma, Hiroyuki Kishi, Atsushi Tajima, Shinji Nakao
Organizer
第60回米国血液学会ASH
Related Report
Int'l Joint Research
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