鉴定与草药和食补充剂诱导的急性肝衰竭相关的遗传风险因素,使用全外测序分析
Tsung-Jen Liao1,2, Menghang Xia2, Dingyin Tao2
1Division of Bioinformatics and Statistics, The FDA's National Center for Toxicological Research, Jefferson, Arkansas.
Gastro hep advances
|December 16, 2025
概括
在HLA和ESRRA基因的遗传变异增加了草药和食补充剂诱导的急性肝衰竭 (HDS-ALF) 的风险. 特定的HLA变异显示出女性特异性关联,这表明HDS-ALF的潜在基于性别的脆弱性.
科学领域:
- 遗传学 是一个遗传学.
- 肝病学 肝病学是一种肝病学.
- 药物基因组学 药物基因组学
背景情况:
- 草药和食补充剂 (HDS) 越来越多地与严重的肝损伤有关,包括急性肝衰竭 (ALF).
- 随着补充剂消费的增加,HDS诱导的ALF (HDS-ALF) 的发生率在全球范围内正在上升.
- 了解对HDS-ALF的遗传倾向对于风险评估和预防至关重要.
研究的目的:
- 为了确定与HDS-ALF相关的遗传风险因素.
- 调查特定基因变异在易受HDS诱导的肝损伤中的作用.
- 根据补充剂类型和性别,探索基因风险的潜在差异.
主要方法:
- 分析了23例HDS-ALF病例的整体外体序列数据.
- 人口控制来自1000个基因组项目.
- 使用严格的P值值 (P < 5 × 10^-8) 确定了统计学上显著的单核酸多态 (SNP),并评估了对等位基频率的稳定性.
主要成果:
- 确定了33个统计学意义上的SNP,主要是在人类白细胞抗原 (HLA) 基因 (HLA-A,HLA-B,HLA-DQA1,HLA-DRB1) 和ESRRA.
- 特定的SNP,包括rs17879990 (HLA-A),rs1131500 (HLA-B) 和rs1161801407 (HLA-DRB1),显示出与HDS-ALF的强烈关联.
- 亚组分析显示,在草药 (4) 和食 (3) 补充剂组中存在显著的SNP,显著的女性特异性关联 (女性15个SNP,男性8个SNP),特别是在HLA-B和HLA-DQA1.
结论:
- 特定的HLA和ESRRA基因变异被确定为HDS-ALF的遗传风险因素.
- 在各种HDS暴露中观察到显著的关联,表明了一般的遗传易感性.
- 这些发现表明潜在的跨性别风险,并突出了与某些HLA和ESRRA变体相关的HDS-ALF的女性特异性脆弱性.
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