结核病史与秘鲁人的遗传调节变异有关
Sara Suliman1,2,3,4, Victor E Nieto-Caballero5,6,7, Samira Asgari1,7,8,9,10,11
1Division of Rheumatology, Inflammation and Immunity, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
medRxiv : the preprint server for health sciences
|July 10, 2023
概括
宿主基因变异影响了Mycobacterium结核病 (Mtb) 感染的结果. 基因表达的变化,特别是在FAH中,将宿主基因与结核病 (TB) 的进展和Mtb感染反应联系起来.
科学领域:
- 免疫学 免疫学 免疫学
- 遗传学 遗传学是一种遗传学.
- 传染性疾病 传染性疾病
背景情况:
- 潜在的Mycobacterium结核病 (Mtb) 感染影响全球四分之一的人口,患有活跃结核病 (TB) 的风险为5-10%.
- 宿主基因变异是影响个体对Mtb感染和结核病进展反应的关键因素.
研究的目的:
- 研究宿主遗传变异与来自秘鲁人口的免疫细胞的基因调节之间的关联,结核病的结果不同.
- 确定表达量的特征位点 (eQTL) 和它们与结核病进展状态的相互作用.
主要方法:
- 招募结核病患者的家庭接触者 (病例和对照).
- 执行了单细胞衍生的树突细胞 (DC) 和巨细胞的转录基因分析,以识别eQTLs.
- 分析了Mtb感染的DCs的公共转录和表观基因组数据.
主要成果:
- 在DC中确定了330个eQTL基因,在巨细胞中确定了257个.
- 在DC中发现了5个基因,其中eQTL变异与结核病进展状态相互作用.
- 发现FAH (fumarylacetoacetate hydrolase) 表达与结核病例的遗传变异相关,并在Mtb感染时下调,并与相关的DNA甲基化变化有关.
结论:
- 主体遗传变异影响免疫细胞中的基因表达,受结核病感染史的影响.
- FAH和氨酸代谢途径与结核病的发病和进展有关.
- 突出了结核病潜在的宿主导治疗点.
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