基因变异是吉尔伯特综合征和HBV感染结果的基础:一个横截面研究
Bilian Yao1, Qi Xu2, Xinxin Zhang2,3,4
1Department of General Practice, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Frontiers in genetics
|November 29, 2023
概括
吉尔伯特综合征的原因UGT1A1的遗传变异与更好的乙型肝炎病毒 (HBV) 感染结果有关. 患有UGT1A1变异的患者的肝硬化和肝细胞癌的发病率降低,这表明有保护作用.
科学领域:
- 肝病学和病毒学.
- 人类遗传学和基因组学
- 药物基因组学 药物基因组学
背景情况:
- 由于不断的细胞损伤,乙型肝炎病毒 (HBV) 感染的预后不佳.
- 胆红素表现出细胞保护性质,这表明它可能在减轻与HBV相关的损害方面发挥作用.
- 由UGT1A1变异引起的吉尔伯特综合征 (GS) 与轻微的非结合性高白血症有关.
研究的目的:
- 研究UGT1A1变异之间的关联,吉尔伯特综合征的遗传基础,以及HBV感染患者的结局.
- 评估UGT1A1基因型对HBV感染个体肝病并发症发展的影响.
主要方法:
- 对2792名患有非结合性高白血病的患者进行了HBV感染和UGT1A1变异的查.
- 在175名确诊暴露于HBV的患者中测序UGT1A1促进体/外因子/内因子区域.
- 在UGT1A1野生型和变种宿主之间比较HBV感染结果,包括肝硬化和肝细胞癌 (LC/HCC).
主要成果:
- 与野生型宿主 (78.95%) 相比,在UGT1A1变异宿主中LC/HCC的发生率显著降低 (13.14%) (p < 0.0001).
- 一种较罕见的UGT1A1变异与LC/HCC诊断时的较高年龄相关 (R = 0.34,p < 0.05).
- 在没有肝硬化的情况下,HBsAg清除仅在UGT1A1变异携带者中观察到 (12.32%vs. 0%).
结论:
- 导致轻度高白血症 (UGT1A1变种) 的先前存在的遗传变异与改善的HBV感染预后有关.
- UGT1A1缺陷的程度与保护作用相关,表明治疗潜力.
- 吉尔伯特综合征的UGT1A1变异可能提供一种保护机制,防止HBV感染的严重后果.
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