ベータブロッカー療法とアンジオテンシン変換酵素のデリレーションポリモルフィズムとの間の薬剤遺伝的相互作用 kongestive heart failure の患者における
D M McNamara1, R Holubkov, K Janosko
1Cardiovascular Institute, University of Pittsburgh Medical Center, Pittsburgh, PA 15213, USA. mcnamaradm@msx.upmc.edu
Circulation
|March 29, 2001
まとめ
ACE Dアレルは,特にベータブロッカー療法なしでは,心不全生存率の悪化と関連しています. ベータブロッカーは,ACE Dアレルの患者のアウトカムに対する負の影響を軽減する可能性があります.
科学分野:
- 心臓病学 心臓病学
- 薬剤遺伝学 薬剤遺伝学について
- 遺伝学 遺伝学とは
背景:
- レーニン・アンジオテンシンと交感神経系の活性化は,心不全の進行に悪影響を及ぼします.
- アンジオテンシン変換酵素 (ACE) 削除 (D) アレルは,レニン-アンジオテンシンシステムの活性化の増加と関連しています.
- ACE Dアレルの患者のアウトカムへの影響と,ベータブロッカー療法との相互作用は十分に理解されていません.
研究 の 目的:
- 静脈機能不全の患者のACE Dアレルと移植なし生存率との関連を調査する.
- 心不全患者におけるACE遺伝子型とベータブロッカー療法の間の潜在的な薬理学的相互作用を評価する.
主な方法:
- 収縮性機能不全の328人の患者の見通しによるフォローアップ.
- ACE D/Iポリモルフィズム (II型,ID型,DD型) に基づいた移植なし生存率の評価.
- ベータブロッカーの治療を受けた患者と受けていない患者の生存率の比較,ACE遺伝子型によって層分化.
主要な成果:
- ACE Dアレルを持つ患者は,移植なしの生存率が著しく低下した (P=0.044).
- ACE Dアルレルの有害効果は,ベータブロッカーを受けていない患者で顕著であった (P=0.005).
- ベータブロッカー (P=0.73) で治療された患者では,ACE遺伝子型が生存に有意な影響を与えないことが観察された (P=0.73).
結論:
- ACE Dアレルは,静脈機能不全の患者の移植なし生存率の低下と関連しています.
- この関連性は,主にベータブロッカーの治療を受けていない患者によって引き起こされる.
- 発見は,心不全管理におけるACE D/Iポリモルフィズムとベータブロッカー療法との間の薬理学的相互作用を示唆しています.
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