核受体中的遗传多态性驱动对环境暴露的反应的变异
Shaoqi Zuo1, Kun Zhang1, Jiayin Dai1
1State Environmental Protection Key Laboratory of Environmental Health Impact Assessment of Emerging Contaminants, School of Environmental Science and Engineering, Shanghai Jiao Tong University, 800 Dongchuan Road, Shanghai 200240, China.
Environmental science & technology
|September 11, 2025
概括
单核酸多态 (SNP) 通过改变核受体功能来影响个人对环境化学物质的反应. 核受体的遗传变异会影响对环境暴露的敏感性,影响人口的健康.
科学领域:
- 基因组学就是基因组学.
- 环境毒理学环境毒理学
- 分子生物学分子生物学
背景情况:
- 已知单核酸多态 (SNP) 影响药物反应和疾病易感性.
- 核受体在调解环境反应中的作用,特别是通过核受体 (NR) 的作用,在很大程度上是未被探索的.
研究的目的:
- 系统地研究SNP在48个NRs的联体结合域 (LBD) 内的SNP对受体-联体相互作用的影响.
- 评估这些遗传变异如何影响对环境化学品的反应.
主要方法:
- 集成的基因组数据库用于在NRLBD中识别误解SNP (小等位基因频率>0.001).
- 采用基于结构的分子对接来评估连接体结合亲缘关系的变化.
- 执行功能验证测试以评估变体受体的转录活性.
主要成果:
- 与野生类型受体相比,在NR LBD中识别了27个误解SNP,与野生类型受体相比,在配体结合亲缘关系中存在显著差异.
- 在对环境化学物质的反应中,证明了与雌激素相关的受体α (ERRα) 和视网膜X受体α (RXRα) 变体的转录活性发生变化.
- 观察到对ERRα变体调节器和RXRα变体减弱激活的不同反应,特别是对有机素化合物.
结论:
- 在NRLBD中的SNP在调节个人和人口对环境暴露的反应方面发挥着关键作用.
- 遗传变异可能导致对环境化学品的敏感性差异.
- 将SNP数据纳入毒理风险评估对于了解环境健康影响至关重要.
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