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アナセトラピブに対するADCY9遺伝子型の影響

Jemma C Hopewell¹, Maysson Ibrahim¹, Michael Hill^1,2

¹Clinical Trial Service Unit and Epidemiological Studies Unit (J.C.H., M.I., M.H., L.B., M.J.L., R.C.), Nuffield Department of Population Health, University of Oxford, United Kingdom.

|July 24, 2019

まとめ

この研究では,ADCY9遺伝子型に基づくコレステロールエステル移転タンパク質 (CETP) 阻害剤アナセトラピブの有効性において,動脈硬化性血管疾患の患者において有意な差異は認められなかった. ADCY9遺伝子型は,アナセトラピブに重大な影響を及ぼさないようです.

科学分野:

心血管医学
薬剤遺伝学
遺伝学

背景:

探索的分析により,ADCY9遺伝子型とコレステリルエステル移転タンパク質 (CETP) 阻害剤治療に対する反応の関連が示唆された.
REVEAL試験では,CETP阻害剤アナセトラピブが動脈硬化性血管疾患の患者に臨床的に有効であることが示されました.

研究の目的:

REVEAL試験におけるアナセトラピブ反応に対するADCY9遺伝子型の影響を調査する.
動脈硬化性血管疾患の患者におけるアナセトラピブの臨床効果にADCY9遺伝子型が影響するかどうかを判断する.

主な方法:

REVEAL試験では,ランダム化され,プラセボ対照試験が実施されました.
安定した動脈硬化性血管疾患の被験者は,強度のアトルバスタチン療法と共にアナセトラピブまたはプラセボを投与された.
アナセトラピブ配分とADCY9 rs1967309遺伝子型との相互作用が主要な血管疾患に及ぼす影響を分析した.

主要な成果:

異なるADCY9遺伝子型 (GG,AG,AA) において,アナセトラピブによる主要な血管疾患の比率的な減少において,有意な差異は認められなかった.
相互作用の遺伝子型P値は0. 96で,統計的に有意な薬理学的効果は示されなかった.
ADCY9遺伝子型と特定の血管イベント成分またはアナセトラピブに対する脂質反応の減少との間には関連性が見つかりませんでした.

結論:

この薬学的相互作用に関する最大規模の研究であるREVEAL試験は,ADCY9遺伝子型がアナセトラピブの臨床効果に関連しているという仮説を裏付けていない.
ダルセトラピブなどの他のCETP阻害剤との潜在的薬理学的相互作用を確認するために,現在進行中のdal- GenE研究などのさらなる研究が必要です.

キーワード:

アデニラートサイクラゼ9 アナセトラピブコレステロールエステル転送タンパク質薬剤遺伝学ランダム化制御試験

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