炎症性サイトカインは脳卒中と脳血管疾患の危険因子に関連している:メンデルのランダム化研究

Zidong Li¹, Yingxuan Guo¹, Shuai Zhu²

¹Department of Neurology and Psychiatry, Beijing Shijitan Hospital, Capital Medical University, No. 10 Tieyi Road, Beijing, 100038, China.

Mammalian genome : official journal of the International Mammalian Genome Society

|August 22, 2025

まとめ

線維細胞成長因子5 (FGF5) の上昇は,血性脳卒中および出血性脳卒中のリスクの増加と関連しています. この炎症性サイトカインは,高血圧と心房細動によって媒介される脳血管疾患の重要な危険因子である可能性があります.

科学分野:

遺伝学
心血管医学
神経科学

背景:

脳卒中のサブタイプとアウトカムにおける炎症性サイトカインの正確な役割は不明である.
これらの関係を理解することは,脳血管疾患の標的型予防と治療戦略の開発に不可欠です.

研究の目的:

メンデルのランダム化を用いて,炎症性サイトカインと脳卒中サブタイプ (病性および出血性) の双方向的因果関係を調査する.
血性脳卒中における機能的アウトカムとサイトカインの関連性を評価し,仲介要因を探求する.

主な方法:

大規模な全ゲノム関連研究データセット (GISCOME,UK Biobank,deCODE,ONTIME) でメンデルのランダム化 (MR) を利用した.
コロカライゼーションとメタ分析を行い,因果関係を確認し,遺伝的根拠を共有した.
高血圧や心房細動などのリスク因子のメディエーション分析のために,2段階の多変量MRを使用した.

主要な成果:

循環性線維細胞成長因子5 (FGF5) の遺伝的予測は,不全性脳卒中と頭蓋内出血の両方のリスクの増加との因果関係を示した.
FGF5 と機能的アウトカム (修正ランキンスケールスコア) の間に有意な関連性が見つかりませんでした.
コロカライゼーションとメタ解析は,共通の単核型多形性 (SNP) を有するFGF5と脳卒中亜型との強い因果関係を確認した.
FGF5に関連した脳卒中リスクの主要なメディエーターとして,メディエーション分析により,エッセンシャル高血圧と心房細動が特定されました.

結論:

循環性線維細胞成長因子5 (FGF5) は脳卒中の潜在的な危険因子であり,特に不血性および出血性サブタイプのリスクを高めます.
エッセンシャル高血圧と心房細動は,FGF5と脳卒中との関係において仲介的な役割を果たします.
炎症性サイトカインは,FGF5によって示され,脳卒中の病原性とそれに関連する危険因子に関与しています.

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