循環中のサイトカインと脳卒中リスクの遺伝的に決定されたレベル
Marios K Georgakis1,2, Dipender Gill3, Kristiina Rannikmäe4
1Institute for Stroke and Dementia Research, University Hospital of Ludwig-Maximilians-University, Munich, Germany (M.K.G., J.B., R.M., M.D.).
Circulation
|December 28, 2018
まとめ
単細胞化学誘導タンパク質-1 (MCP-1) の遺伝的に高いレベルは,脳卒中,特に大動脈および心臓栓塞性脳卒中のリスクを増大させます. MCP-1を標的にすることで脳卒中を予防できるかどうかを判断するには,さらなる研究が必要である.
科学分野:
- 心血管遺伝学
- 脳卒中の病因
- 炎症バイオマーカー
背景:
- サイトカインと成長因子は,血管疾患の発生に関与しています.
- 観察研究では,循環中のサイトカイン/成長因子レベルと脳卒中リスクとの関連が示唆されています.
- 脳卒中におけるこれらの因子の遺伝的に決定されたレベルの役割は,さらなる調査を必要としています.
研究 の 目的:
- 遺伝的に決定された循環中のサイトカインと成長因子のレベルと脳卒中のリスクとその病因的なサブタイプとの関連を調べる.
- 2つのサンプルのメンデルのランダム化アプローチを使用して因果関係を評価する.
主な方法:
- ゲノム全体の関連研究データを用いて,2つのサンプルによるメンデルのランダム化研究が行われました.
- 41のサイトカインと成長因子の遺伝的手段は,健康な大人のコホートから得られた.
- 脳卒中と脳卒中サブタイプとの関連は,MEGASTROKEデータセットで評価され,UK Biobankで検証されました.
主要な成果:
- 単細胞化学誘致タンパク質-1 (MCP- 1/ CCL2) のレベルが高くなる遺伝的傾向は,脳卒中,血栓性脳卒中,大動脈性脳卒中,心臓栓塞性脳卒中のリスクの増加と関連していました.
- 小血管性脳卒中や脳内出血の有意な関連性は見つかりませんでした.
- 冠動脈疾患と心筋梗塞と関連しているが,心房細動とは関連していない.
結論:
- 遺伝的に決定されたMCP-1濃度の上昇は,脳卒中,特に大動脈および心臓栓塞性脳卒中のリスクが高くなります.
- この発見は,MCP-1が脳卒中の病原性において潜在的因果的な役割を果たすことを示唆している.
- MCP-1またはその受容体を標的とした治療戦略を探るため,さらなる研究が必要である.
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