从参与者获得的细胞系转录组分析和小鼠研究表明,ZNF335在血胆固醇对他类药物反应中的作用
Elizabeth Theusch1, Flora Y Ting1, Yuanyuan Qin1
1Department of Pediatrics, University of California San Francisco, Oakland, CA USA.
bioRxiv : the preprint server for biology
|July 3, 2023
概括
这项研究确定ZNF335是一种影响他类药物降低胆固醇有效性的新型基因. ZNF335的遗传变异可能解释了为什么一些人对他类药物治疗的反应不同.
科学领域:
- 药物基因组学 药物基因组学
- 心血管研究研究心血管研究
- 分子生物学分子生物学
背景情况:
- 类药物通过降低低密度脂蛋白胆固醇 (LDLC) 有效降低心血管疾病风险.
- 在他类药物的疗效方面存在显著的个体间变异性,潜在的遗传因素在很大程度上无法解释.
研究的目的:
- 发现调节他类药物诱导的LDLC减少的新基因.
- 研究ZNF335在胆固醇代谢和他类药物的反应中的作用.
主要方法:
- 从接受他类药物治疗的参与者的淋巴细胞细胞系 (LCL) 的RNA测序.
- 在胆固醇和药物遗传学 (CAP) 试验中,LCL基因表达变化与血LDLC反应的相关性.
- 使用Zfp335突变小鼠进行体内验证,以评估胆固醇水平和他类药物反应.
主要成果:
- 147个人类基因显示,LCL表达变化和血LDLC对他类药物反应之间存在显著的相关性.
- ZNF335和CNOT3表现出最强的相关性.
- Zfp335突变小鼠的胆固醇水平发生变化,LDL对他类药物的反应减弱,特别是在雄性中.
结论:
- ZNF335被确定为血胆固醇和他类药物反应的新型调节剂.
- ZNF335的遗传变异可能导致观察到的他类药物疗效的个体间差异.
关键词:
通过RNA测序来测序RNA序列.史塔丁类药物是一种胆固醇 胆固醇 胆固醇 是一种基因表达的基因表达方式蛋白质脂质蛋白质 (lipoprotein) 是一种脂肪蛋白质.淋巴细胞细胞系的细胞系.鼠标 鼠标 鼠标 鼠标指蛋白 335 指蛋白 335 指蛋白更多相关视频
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