ダビガトランの血濃度の遺伝的決定因子とその出血との関係
Guillaume Paré1, Niclas Eriksson, Thorsten Lehr
1Population Health Research Institute, Hamilton Health Sciences and McMaster University, David Braley Cardiac Vascular and Stroke Research Institute, 237 Barton St E, Room C3-103, Hamilton, ON, Canada L8L 2X2. pareg@McMaster.ca
Circulation
|March 8, 2013
まとめ
遺伝的変異はダビガトランの濃度と出血リスクに影響します. CES1 rs2244613ポリモルフィズムは,心房細動患者における薬剤曝露の低下と出血の減少に関連しています.
科学分野:
- ファルマコゲノミクスとは
- 心血管医学は,心臓血管医学である.
- 遺伝学 遺伝学とは
背景:
- ダビガトランのエテキサートは,ウォルファリンと比較して良好な安全性プロファイルで,心房細動における脳卒中予防に有効です.
- ダビガトランの濃度における個体間の変動性は,遺伝的要因が関与していることを示唆している.
- 遺伝子の影響を調査することで,ダビガトランの治療と患者の治療結果を最適化することができます.
研究 の 目的:
- ダビガトランの濃度と臨床結果に関連した遺伝的変異を特定する.
- ダビガトランの安全性と有効性に対する遺伝子変異の影響を調査する.
- ダビガトランの治療に対する反応における個体間の違いを理解する.
主な方法:
- ゲノム・ワイド・アソシエーション・スタディ (GWAS) は,長期抗凝固療法 (RE-LY) のランダム化評価試験 (Randomized Evaluation of Long-term Anticoagulation Therapy) の2944人の参加者に実施されました.
- CES1 rs2244613,ABCB1 rs4148738,CES1 rs8192935.3 を含む単核酸多形態 (SNP) の分析について
- 遺伝子変異,ダビガトランの最低濃度およびピーク濃度,出血 / 血行不全事件の間の関連性の統計的評価.
主要な成果:
- CES1 SNP rs2244613は,ダビガトランの最低濃度を下げることと,出血のリスクの低下と有意に関連していました.
- CES1 rs2244613マイナーアレル (32.8%の患者) の存在は,アレル毎の最低濃度の15%の減少と相関していました.
- CES1 rs2244613マイナーアレルのキャリアは,ワルファリンと比較してダビガトランの投与で出血が著しく減少した.
- 研究された遺伝的変異体と不血症イベントとの間に有意な関連性が見つかりませんでした.
結論:
- CES1 rs2244613ポリモルフィズムは,ダビガトランの曝露と出血リスクの重要な決定因子です.
- 遺伝子プロファイリング,特にCES1 rs2244613の遺伝子プロファイリングは,ダビガトランの治療をパーソナライズするのに役立ちます.
- 研究結果は,抗凝固剤治療戦略の最適化において,薬剤遺伝学が果たす役割を支持しています.
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