2011 Fiscal Year Final Research Report
Association of genotypes for drug-binding protein with anti-cancer drug responses
| Project/Area Number |
21590191
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Medical pharmacy
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| Research Institution | National Institute of Health Sciences |
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Principal Investigator |
SAI Kimie 国立医薬品食品衛生研究所, 医薬安全科学部, 室長 (20195960)
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| Co-Investigator(Kenkyū-buntansha) |
KATORI Noriko 国立医薬品食品衛生研究所, 薬品部, 室長 (60142121)
KUROSE Koichi 国立医薬品食品衛生研究所, 医薬安全科学部, 室長 (30280754)
SAITO Yoshiro 国立医薬品食品衛生研究所, 医薬安全科学部, 部長 (50215571)
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| Project Period (FY) |
2009 – 2011
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| Keywords | オーダーメード医療 / α-1-酸性糖蛋白 / 薬剤反応性 / 遺伝子多型 / ハプロタイプ |
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| Research Abstract |
This study was aimed to identify genetic polymorphisms of ORM genes(ORM1 and ORM2), encodingα-1-acid glycoprotein(AGP), which might affect anti-cancer drug responses. Detailed analysis on ORM gene structures(duplication/deletion) and genetic polymorphisms/haplotypes were conducted for Japanese cancer patients who received paclitaxel(PTX)-therapy, and the association of ORM genotypes with serum AGP levels and PTX-pharmacokinetics were investigated. As a result, ORM genetic polymorphisms related to increased levels of serum AGP and the area under the plasma concentration-time curves of PTX-metabolites were identified. A luciferase reporter gene assay indicated existence of putative promoter regions which might be responsible for different regulatory mechanisms of gene expression between ORM1 and ORM2.Possible influence of the ORM genetic polymorphism on the reporter activity was also examined.
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