パラオキソナゼ1 (PON1) 遺伝子ポリモルフィズムと機能的活性と,全身の酸化ストレスと心血管リスクとの関連
Tamali Bhattacharyya1, Stephen J Nicholls, Eric J Topol
1Department of Cell Biology, Cleveland Clinic, Cleveland, Ohio 44195, USA.
JAMA
|March 20, 2008
まとめ
パラオキソナーゼ1 (PON1) 遺伝子型が活性に影響し,酸化ストレスと心血管疾患のリスクに影響します. 低PON1活性および特定のゲノタイプは,死亡率の上昇と主要な不良心疾患に関連しています.
科学分野:
- バイオケミストリー バイオケミストリー
- 遺伝学 遺伝学とは
- 心臓病学 心臓病学
背景:
- パラオキソナーゼ1 (PON1) は,抗酸化物質と心臓を保護する性質を示しています.
- PON1遺伝子型,活動,酸化ストレス,心血管疾患 (CVD) のリスクの相互作用は,体系的な調査を必要としています.
研究 の 目的:
- PON1活動の遺伝的および生化学的要因と全身的酸化ストレスマーカーおよびヒトにおけるCVDリスクとの関連性を調査する.
主な方法:
- PON1活動,Q192Rポリモルフィズム,CVDの流行,および将来の主要な不良心事との関連性について,冠動脈血管撮影を受けた1399人の患者を評価した.
- マススペクトロメトリーによる脂肪酸酸化産物の全身レベルを150人のマッチした患者で測定し,PON1の遺伝子型と活性に基づいて比較した.
主要な成果:
- PON1遺伝子型 (QQ192 > QR192 > RR192) は,PON1の活性低下と全身の酸化ストレス増加と相関しています.
- QQ192遺伝子型は,RR192/QR192.2と比較して,全因死亡率 (aHR,2.05) と主要な心疾患不良事象 (aHR,1.48) のリスクが高かった.
- 最も高いPON1アクティビティクォーティルは,最も低いクォーティル (23.5-25.1%) と比較して,重大な心疾患の有害事象発生率 (7.3-7.7%) を著しく低下させた.
結論:
- PON1の遺伝的決定因子,活動,全身的酸化ストレス,および将来の心血管リスクとの間にメカニズム的な関連が確立されました.
- PON1の動脈保護機能の潜在的なメカニズムを示唆しています.
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