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与线粒体相关的核基因中的蛋白质截断变体和慢性肝病风险
Huangbo Yuan1, Zhenqiu Liu1, Mingyang Chen1
1State Key Laboratory of Genetic Engineering, Human Phenome Institute, Zhangjiang Fudan International Innovation Center, and School of Life Sciences, Fudan University, No. 2005 Songhu Road, Shanghai, 200438, China.
BMC medicine
|June 11, 2024
概括
线粒体基因中的蛋白质截断变体 (PTV) 显著增加肝病风险. 这些遗传变异与较高的肝纤维化,癌症和死亡风险有关,有助于早期干预策略.
科学领域:
- 遗传学和基因组学 遗传学和基因组学
- 肝病学 肝病学是一种肝病学.
- 线粒体生物学 线粒体生物学
背景情况:
- 线粒体功能障碍是肝脏疾病的关键因素.
- 关于肝病风险的线粒体基因中蛋白质截断变体 (PTV) 的作用尚未得到充分探索.
研究的目的:
- 研究与线粒体相关基因中的PTVs与肝功能障碍和慢性肝病的风险之间的关联.
- 为了确定特定的PTV及其对肝病结果的影响.
主要方法:
- 分析了442,603名英国生物库参与者的全外组测序数据.
- 在2466个线粒体相关基因中提取了60,928个PTV.
- 研究了与肝脏生物标志物,慢性肝脏疾病和与肝脏相关的死亡率的关联.
主要成果:
- 866个PTV与肝功能障碍显著相关,主要影响代谢途径.
- 这些PTV的携带者显示显著增加风险:纤维化/肝硬化5.33倍,肝癌2.82倍,肝病死亡率4.41倍.
- 这些关联在各种人口统计和临床子组中保持一致.
结论:
- 线粒体相关基因中的PTV对肝病风险有很大影响.
- 识别这些变异的携带者可以帮助风险分层和早期临床干预肝脏疾病.
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