システィック・フィブロシスにおける肝疾患の遺伝子変形剤
Jaclyn R Bartlett1, Kenneth J Friedman, Simon C Ling
1Cystic Fibrosis/Pulmonary Research and Treatment Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
JAMA
|September 10, 2009
まとめ
SERPINA1 Zアレルは,システィックフィブロシス (CF) 患者における重度の肝疾患の重要な危険因子です. このアレルを持つ個人は,この合併症を発症するリスクが約5倍に増加します.
科学分野:
- 遺伝学 遺伝学とは
- 肝臓病理学 肝臓病理学
- 肺内科 肺内科 肺内科
背景:
- 胞性線維症 (CF) は複数の臓器に影響を与え,重度の肝疾患とポータル高血圧を発症する患者のサブセットがあります.
- CFの合併症に影響を与える遺伝的要因を特定することは,パーソナライズされた医療にとって極めて重要です.
研究 の 目的:
- 5つの候補遺伝子のポリモルフィズムとCF患者の重度の肝疾患の発症との関連性を調査する.
- 具体的には,アルファ(1) -アンチトリプシン (SERPINA1),アンジオテンシン変換酵素 (ACE),グルタチオンSトランスファーゼ (GSTP1),マンノース結合レクチン2 (MBL2) と成長変容因子ベータ1 (TGFB1) を調べました.
主な方法:
- 2段階の症例対照研究で,重度の肝疾患を患った患者と,重度の肝疾患を患っていない患者と,複数の国際センターで実施した.
- 候補遺伝子の9つのポリモルフィスムのゲノタイプ化.
- 遺伝子型と疾患状態の関連性を特定するためのロジスティック回帰分析.
主要な成果:
- SERPINA1 Zアレルは,初期段階と複製段階の両方で重度の肝疾患と強く関連していました.
- TGFB1コドン10 CC遺伝子型は,初期研究で関連性を示したが,複製段階ではそうではなかった.
- 組み合わせた分析は,SERPINA1 ZアレルとCF関連の肝疾患 (OR, 5.04; P = 1.5 x 10(-8) の間の有意な関連性を確認しました.
結論:
- SERPINA1 Zアレルは,システィック線維症における重度の肝疾患の確認された危険因子です.
- SERPINA1 Zアレルを持ち歩くCFの患者は,肝臓合併症を発症するリスクが大幅に増加しています.
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