マイクロソーマルエポキシドヒドロラゼの遺伝子におけるポリモルフィズムとエンフィゼマの感受性との関連
1Department of Pathology, University of Edinburgh, UK.
Lancet (London, England)
|August 30, 1997
まとめ
マイクロソーマルエポキシドヒドロラーゼ (mEPHX) の遺伝的変異は,慢性閉塞性肺疾患 (COPD) と肺腫に対する感受性に影響します. mEPHXの活性が遅い個人は,これらの肺疾患のリスクが増加しています.
科学分野:
- 肺医学 肺医学について
- 遺伝学 遺伝学とは
- 毒理学 毒理学 毒理学
背景:
- 異質化合物の肺のファーストパス代謝は,酸化ストレスからの保護に不可欠です.
- 微小体エポキシドヒドロラーゼ (mEPHX) は,この保護機構に役割を果たしています.
- mEPHXの遺伝的変異は,肺疾患に対する感受性に影響を与える可能性があります.
研究 の 目的:
- mEPHX遺伝子ポリモルフィズムと慢性閉塞性肺疾患 (COPD) と肺気腫の感受性との関連を調べる.
- mEPHXの遅いまたは速い活性型がこれらの肺疾患を発症するリスクに影響するかどうかを判断する.
主な方法:
- 遅いおよび速いmEPHX活性変種を特定するためのPCRベースの遺伝子型測定法を開発しました.
- ゲノタイプ化された203人の献血者対照群と,喘息,肺がん,慢性肺炎,肺腫の患者グループ.
- 病状との関係で遺伝子型頻度を分析した.
主要な成果:
- コントロールと比較して,COPDと肺腫のグループでは,生まれながらの遅いmEPHX活性 (ホモジゴット) を有する個体の割合が著しく高かった.
- ホモジゴス・スロー・アクティビティの確率比率は,COPDでは4.1,エムフィゼマでは5.0であり,リスクが増加していることを示している.
- これらの発見は,mEPHXの活動に関連したCOPDとエムフィゼマの遺伝的傾向を示唆しています.
結論:
- mEPHXのような異種生物を代謝する酵素における遺伝的多形態化は,酸化物質に関連する肺疾患に対する個々の感受性に寄与する可能性があります.
- 煙草の煙のエポキシド誘導体は,COPDとエムフィゼマの特徴である肺損傷に関与している可能性があります.
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