心血管疾患の予測のための大規模プロテオミクスの評価
Hannes Helgason1,2, Thjodbjorg Eiriksdottir1, Magnus O Ulfarsson1,2
1deCODE genetics/Amgen, Inc, Reykjavik, Iceland.
JAMA
|August 22, 2023
まとめ
新種のタンパク質リスクスコアは,動脈硬化性心血管疾患 (ASCVD) のリスクを評価するのに有望である. このスコアは,既存の臨床的要因と多遺伝子リスクスコアと組み合わせると,リスク予測の精度がわずかに向上します.
科学分野:
- 心血管医学
- プロテオミクス
- 遺伝学
背景:
- 動脈硬化性心血管疾患 (ASCVD) は,世界中で主要な死因となっています.
- 現在のリスク評価モデルは臨床的要因と多遺伝子リスクスコアに依存しているが,その予測力は限られている.
- ASCVDリスクの予測を高めるためのプラズマのタンパク質バイオマーカーの有用性は,活発な調査分野です.
研究 の 目的:
- ASCVDイベントを予測するためのタンパク質リスクスコアを開発し,検証する.
- タンパク質リスクスコアと伝統的な臨床リスク要因と多遺伝子リスクスコアを比較する.
- タンパク質リスクスコアの追加値を評価する.
主な方法:
- アイスランドのプライマリイベント集団 (13,540 個) のプロテオミクスデータによる遡及分析.
- 安定したASCVDを持つ臨床試験 (6,791人) の二次イベント集団の分析.
- 4963の血タンパク質濃度を用いたタンパク質リスクスコアの開発;多遺伝子リスクスコアと臨床的要因 (年齢,性別,スタチンの使用,高血圧,糖尿病,BMI,喫煙) との比較.
主要な成果:
- タンパク質リスクスコアは,原発的 (HR1. 93/ SD) と二次的 (HR1. 62/ SD) 集団の両方でASCVDイベントと有意な関連性を示した.
- 臨床リスク因子モデルにタンパク質リスクスコアを追加すると,差別性が著しく改善された (C指数は0. 014- 0. 022増加).
- タンパク質リスクスコアも二次集団の異なる祖先との間に有意な関連性を示した.
結論:
- プラズマプロテオミクスから得られたタンパク質リスクスコアは,ASCVDの重要な予測因子です.
- タンパク質リスクスコアと臨床リスクスコアとポリジェニックリスクスコアを統合すると,リスク予測のわずかな,しかし統計的に有意な改善が得られます.
- これらの発見は,タンパク質リスクスコアが現在のASCVDリスク評価戦略に価値ある追加となる可能性があることを示唆しています.
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