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Brian A Ference1,2,3, John J P Kastelein4, Kausik K Ray5

  • 1Centre for Naturally Randomized Trials, University of Cambridge, Cambridge, United Kingdom.

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|January 30, 2019
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血トリグリセリドまたはLDL- Cの低下は,両方がアポリポプロテインB (ApoB) と関連しているため,心臓血管リスクに類似した利点があります. これらの脂質の減少による臨床的利益は,ApoB濃度の減少に比例しているようです.

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科学分野:

  • 心血管遺伝学
  • 脂質代謝
  • 遺伝的流行病学

背景:

  • トリグリセリドとコレステロールは,アポリプロテインB (ApoB) を含むリポプロテインによって運ばれます.
  • 低密度脂質タンパク質コレステロール (LDL- C) と対照的に血トリグリセリドを低下させることが心血管疾患のリスクに及ぼす影響は不明である.

研究 の 目的:

  • トリグリセリド値を下げる変種 (リポタンパク質リパース遺伝子,LPL) とLDL-C値を下げる変種 (LDL受容体遺伝子,LDLR) と心血管疾患リスクとの関連を ApoBの単位変化で比較する.
  • 心血管リスクに対するトリグリセリドとLDL-Cの独立した貢献を調査する.

主な方法:

  • メンデルのランダム化分析は,LPLとLDLRの遺伝子スコアを用いて行われました.
  • 北米とヨーロッパの63のコホートと症例対照研究 (N=654,783; 91,129のCHD症例) のデータを分析した.
  • 血脂レベル (トリグリセリド,LDL- C,ApoB) と冠動脈疾患 (CHD) のリスクとの関連が評価されました.

主要な成果:

  • LPLとLDLRの両方の遺伝子スコアは,ApoBの10 mg/ dLの減少ごとに,CHDリスクの同様の減少と関連していました.
  • LPLの変種はトリグリセリドを大幅に低下させ,LDLCをわずかに増加させ,LDLRの変種はLDLCとトリグリセリドを低下させました.
  • ApoBを調整すると,トリグリセリドとLDL- CのレベルとCHDリスクの関連は非有意となり,ApoBが主要なメディエーターであることを示した.

結論:

  • トリグリセリドを低下させるLPL変種とLDL-Cを低下させるLDLR変種は,ApoBの単位変化ごとに同様の心血管保護を与える.
  • トリグリセリドとLDL- Cの低下による臨床的利益は,ApoBの絶対値の低下に比例する可能性がある.
  • ApoBは,脂質低下戦略の心血管上の利点を評価するための統一的なターゲットを表しています.