中东卡塔尔人口中TNF抑制剂的药物基因组景观
Zainab Jan1, Dinesh Velayutham1,
1College of Health & Life Sciences, Hamad Bin Khalifa University, Education City, Doha, Qatar.
Frontiers in immunology
|December 5, 2025
概括
遗传变异显著影响瘤坏死因子抑制剂 (TNFi) 反应. 这项研究揭示了卡塔尔人的特异性TNFi药物基因组变异频率,这对于了解中东人口的治疗变异性至关重要.
科学领域:
- 药物基因组学 药物基因组学
- 自免疫性疾病 自免疫性疾病
- 遗传学 是一个遗传学.
背景情况:
- 瘤亡因子α (TNF-α) 是自身免疫性疾病中的关键细胞因子.
- TNF抑制剂 (TNFi) 治疗这些疾病,但40%的患者由于遗传因素而表现出不良反应.
- 缺乏对影响中东人口TNFi反应的遗传变异的理解.
研究的目的:
- 研究影响卡塔尔人TNFi反应的遗传变异分布.
- 为了将这些变异与全球等位基因频率进行比较.
- 为了确定与TNFi治疗结果相关的特定变异和基因,在这个代表性不足的人群中.
主要方法:
- 分析了14387名卡塔尔人的全基因组测序数据.
- 评估了与TNFi反应相关的111个基因.
- 已知151种药物基因组变异的等位基因频率与gnomAD数据集进行了比较.
主要成果:
- 在已知的TNFi药基因组变异中,大约有一半在卡塔尔与全球人口相比显示出明显不同的等位基因频率.
- 观察到高频率的rs1800629 (TNF),rs1800896 (IL10) 和rs1143634 (IL1B) 变体,与乙素和因弗力西马布反应相关.
- 确定PSORS1C1具有与Etanercept和Adalimumab反应相关的功能丧失变体的最高累积等位基因概率.
结论:
- 这项研究为卡塔尔TNFi的药物基因组学提供了关键的见解.
- 研究结果突出了影响中东人口TNFi反应的遗传变异.
- 这项研究支持在代表性不足的群体中研究遗传学,并可以为个性化医疗方法提供信息.
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