プラズマのHDLコレステロールと心筋梗塞のリスク:メンデルのランダム化研究
Benjamin F Voight1, Gina M Peloso, Marju Orho-Melander
1Department of Pharmacology, University of Pennsylvania, Philadelphia, PA, USA.
Lancet (London, England)
|May 22, 2012
まとめ
高密度脂質タンパク質 (HDL) コレステロールは心臓発作リスクの低下と関連していますが,この研究では,HDLを上昇させるいくつかの遺伝的方法が心筋梗塞のリスクを軽減しないことを示しています. これは,高いHDLは常に心臓発作のリスクが低いことを意味するという考えに挑戦しています.
科学分野:
- 心血管遺伝学 心血管遺伝学
- バイオマーカーの因果関係
- 心筋梗塞のリスク因子 心筋梗塞のリスク因子
背景:
- 高血圧のHDLコレステロールは,心筋梗塞のリスクの低下と関連しています.
- HDLコレステロールと心筋梗塞の因果関係は不明である.
- メンデルのランダム化は,混同因子から独立して,バイオマーカーの因果関係を評価するための堅実な方法である.
研究 の 目的:
- メンデルのランダム化を使用して,心筋梗塞のリスクに対するプラズマHDLコレステロールの因果関係を調査する.
- HDLコレステロールレベルに影響を及ぼす遺伝的変異が因果的に心筋梗塞のリスクを低下させるかどうかをテストする.
主な方法:
- 2つのメンデルのランダム化分析が行われました.
- 分析1:LIPG遺伝子 (LIPG Asn396Ser) の単一核酸多形態 (SNP) を道具として使用した.
- 分析2:HDLコレステロールと限定的に関連した14の一般的なSNPの遺伝子スコアを使用した. 陽性対照として,LDLコレステロールの遺伝子スコアが使用されました.
主要な成果:
- LIPG396SerアレルはHDLコレステロールを増加させましたが,心筋梗塞のリスク (OR 0.99,95%CI 0.88-1.11) と関連しませんでした.
- HDLコレステロールの遺伝子スコアは,心筋梗塞のリスクの低下との関連を示さなかった (OR 0.93,95%CI 0.68-1.26).
- LDLコレステロールの遺伝子スコアは,心筋梗塞のリスクと一致する関連性を示しました (OR 2.13,95%CI 1.69-2.69).
結論:
- 血のHDLコレステロールを上昇させる特定の遺伝的メカニズムは,心筋梗塞のリスクを下げるようには見えません.
- これらの発見は,プラズマのHDLコレステロールの増加が均一に心筋梗塞のリスクを減少させるという仮定に異議を唱える.
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