与肝脏脂肪相关的不同遗传变异及其与心血管疾病和癌症的对比关系
Altayeb Ahmed1, Madeleine Cule2, Jimmy D Bell3
1Joseph Banks Laboratories, College of Health and Science, University of Lincoln, Lincoln, UK.
Journal of hepatology
|July 3, 2024
概括
肝脏脂肪的积累对健康有多种影响. 虽然一些机制可能会降低心血管风险,但过多的肝脂肪与肝硬化和癌症风险增加有关,无论原因如何.
科学领域:
- 遗传学和心血管疾病
- 肝病学和癌症生物学 肝病学和癌症生物学
- 代谢综合征研究 代谢综合征研究
背景情况:
- 脂肪性肝病 (脂肪肝) 和心血管/癌症结局之间的联系尚不清楚.
- 调查因果机制需要了解肝脏脂肪的多种影响.
研究的目的:
- 通过MRI衍生脂肪测量和遗传学来探索肝脏脂肪和健康结果之间的因果关系.
- 区分各种肝脏脂肪积累机制对疾病风险的影响.
主要方法:
- 在37358名英国生物库参与者的全基因组关联研究 (GWAS) 中,确定了与肝脏脂肪相关的遗传变异.
- 门德尔随机化研究了肝脏脂肪对健康结果的因果作用,调整了BMI,酒精和脂质,使用GWAS和FinnGen数据.
主要成果:
- 与肝脏脂肪相关的13种遗传变异显示出不同的健康结果关联.
- 肝脏甘油出口受损与心血管疾病风险降低相关,但增加了2型糖尿病风险.
- 增强的新生脂质生成与更高的心血管疾病风险相关.
- 遗传上较高的肝脂肪含量导致肝硬化,肝细胞癌和胆道/胆囊癌的风险增加,这种风险取决于剂量,不论机制如何.
结论:
- 肝脂肪对心血管疾病的影响依赖于机制,挑战其作为独立风险因素的作用.
- 过多的肝脂肪,无论机制如何,都与肝硬化和癌症有因果关系,这种关系取决于剂量.
- 结果支持个性化管理和脂肪肝疾病风险评估.
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