ヒトにおけるサイトカイン生成の変動を理解するための機能的ゲノム学のアプローチ
Yang Li1, Marije Oosting2, Sanne P Smeekens2
1Department of Genetics, University Medical Center Groningen, University of Groningen, 9700 RB Groningen, the Netherlands.
Cell
|November 5, 2016
まとめ
遺伝的要因は免疫反応に大きく影響し,サイトカインの産生に影響します. この研究では,免疫媒介性疾患や感染症に関連した新しい遺伝子変異が特定されました.
科学分野:
- 人間の機能ゲノミクス
- 免疫学
- 遺伝学
背景:
- 免疫反応の変動性は,健康と病気を理解するために重要です.
- 遺伝的要因は免疫系の機能に影響することが知られている.
研究 の 目的:
- 様々な刺激に対する反応として サイトカインの産生に影響する遺伝的変異を調査する.
- 免疫反応の多様性との新しい遺伝的関連を特定する.
主な方法:
- 2つの独立したコホート (500人と200人の健康な個体) の分析
- 細菌,真菌,ウイルス,および非微生物剤による刺激後のex vivoサイトカイン生成を調査した.
- サイトカイン定量特征局 (cQTLs) を特定するために,全ゲノム関連研究を利用した.
主要な成果:
- サイトカインの生産能力に影響を与える強い遺伝的遺伝性を示した.
- 17つの新しい全ゲノム有意のサイトカインQTL (cQTL) が特定されました.
- パターン認識受容体,シトカイン/コンプリメント阻害体,カルリクレイン系などの経路で,また感染や免疫媒介疾患に関連するSNPの間で,cQTLの濃縮が発見されました.
結論:
- 遺伝的変異は個々のサイトカインの生産レベルを決定する上で重要な役割を果たします.
- 特定されたcQTLは,免疫反応の遺伝的構造についての洞察を提供します.
- サイトカインの産生に影響を与える遺伝因子は,感染症や免疫媒介疾患に対する感受性に関連している.
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