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2018 Fiscal Year Final Research Report

HLA-omics-based pharmacogenomics for adverse drug reactions in genome cohort studies

Research Project

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Project/Area Number 17K19804
Research Category

Grant-in-Aid for Challenging Research (Exploratory)

Allocation TypeMulti-year Fund
Research Field Society medicine, Nursing, and related fields
Research InstitutionKanazawa University

Principal Investigator

Hosomichi Kazuyoshi  金沢大学, 医学系, 准教授 (50420948)

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
Project Period (FY) 2017-06-30 – 2019-03-31
KeywordsHLA / 薬剤副作用 / コホート研究
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.

Free Research Field

ゲノム情報学

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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Published: 2020-03-30  

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