| Project/Area Number |
26670074
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| Research Category |
Grant-in-Aid for Challenging Exploratory Research
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| Allocation Type | Multi-year Fund |
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| Research Field |
Medical pharmacy
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| Research Institution | The University of Tokyo |
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Principal Investigator |
Suzuki Hiroshi 東京大学, 医学部附属病院, 教授 (80206523)
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| Co-Investigator(Kenkyū-buntansha) |
HONMA Masashi 東京大学, 医学部附属病院, 特任准教授 (60401072)
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| Project Period (FY) |
2014-04-01 – 2016-03-31
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| Project Status |
Completed (Fiscal Year 2015)
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| Budget Amount *help |
¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
Fiscal Year 2015: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2014: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
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| Keywords | 薬剤反応性 / 免疫学 / 生体分子 / トランスレーショナルリサーチ |
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| Outline of Final Research Achievements |
It has been indicated that genetic backgrounds of patients largely affect the risk for idiosyncratic adverse drug reactions. The interaction between HLA-B*57:01 and abacavir was well characterized and it might trigger immune reactions. We examined whether similar "HLA-drug" interactions are observed in the case of seven combinations of HLA-B genotypes and drugs. As a result, only one combination, B*35:05 and nevirapine, showed the strong interaction as observed in B*57:01 and abacavir. It was assumed that nevirapine associates to the antigen presenting pocket of HLA molecule due to the differences in primary sequence of B*35:05 and its negative control. Indeed, the tendency of peptide repertoire presented by B*35:05 changed in the presence of nevirapine. Refolding experiments using denatured HLA protein also supported this interaction.
On the other hand, it would be need to consider different mechanisms of the interaction in other combinations including B*15:02 and carbamazepine.
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