血小板GPIIIa Pl(A) ポリモルフィズムでは,アゴニストに対する異なる感受性が表れます
A D Michelson1, M I Furman, P Goldschmidt-Clermont
1Departments of Medicine and Pathology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Circulation
|March 7, 2000
まとめ
血小板内の Pl (A2) 遺伝子変異は,血小板の反応性と活性化を高めます. 血小板機能におけるこの遺伝的差異は,冠動脈事件への遺伝的傾向を説明する可能性がある.
科学分野:
- 心血管遺伝学 心血管遺伝学
- 血液学 ヘマトロジ
- 分子生物学は分子生物学である.
背景:
- 遺伝的傾向と血小板の過剰反応性は,不全性冠動脈事件と関連しています.
- 血小板機能の遺伝的差異の背後にあるメカニズムは不明である.
- グリコプロテインIIIa (GP IIIa) の Pl(A2) ポリモルフィズムは冠動脈症候群と関連しており,血小板過剰反応におけるその役割に関する調査を促しています.
研究 の 目的:
- Pl(A) (HPA-1) ポリモルフィズムを持つ血小板の機能的パラメータを特徴付ける.
- GP IIIaにおけるLeu (Pl(A1) からPro (Pl(A2) の置換が血小板活性化と機能に与える影響を調査する.
- Pl(A2) 変種が血小板過剰反応に寄与し,抗血小板剤に対する反応に影響を与えるかどうかを判断する.
主な方法:
- 56人の健康なドナーを研究し,Pl (A1,A1),Pl (A1,A2),Pl (A2,A2)) のポリモルフィズムにゲノタイプした.
- 評価された表面発現Pセレクチン,GP IIb/IIIa結合フィブリノゲン,およびアデノシンジフォスファート (ADP) への反応として活性化されたGP IIb/IIIa.
- アスピリンとアブシキシマブに対する血小板集積感受性の評価.
主要な成果:
- Pl(A2) 陽性血小板は,P-セレクチン,フィブリノゲン結合,GP IIb/IIIaの活性化が,Pl(A1,A1) 血小板と比較して,低用量のADP刺激で,P-セレクチン,フィブリノゲン結合,GP IIb/IIIaの活性化が,著しく高い遺伝子用量効果を示した.
- ADP刺激によるGP IIb/IIIaの発現は,Pl(A2,A2) 血小板において有意に高かった.
- Pl (A) アレル (Pl (A1,A2)) に対してヘテロジゴットな血小板は,アスピリンとアブキシマブによる集積抑制に対する感受性の増加を示した.
結論:
- Pl(A2) 陽性血小板は,活性化の値が低下していることを示しています.
- ヘテロツイゴス Pl ((A) 血小板は,一般的な抗血小板薬に対する過敏性が高い.
- これらの in vitro 発見は,in vivo 血栓性疾患と個別化された抗血小板治療の理解に潜在的関連性を示唆しています.
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