结核病史与秘鲁人的遗传调节变异有关
Victor E Nieto-Caballero1,2,3, Josephine F Reijneveld4, Angel Ruvalcaba4
1Division of Immunology, Department of Pediatrics, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts, United States of America.
PLoS genetics
|June 13, 2024
概括
宿主基因变异影响基因调节,影响结核病 (TB) 疾病风险. 我们在秘鲁人群中发现了与结核病进展相关的FAH基因表达变化,这表明了新的研究途径.
科学领域:
- 遗传学和免疫学 遗传学和免疫学
- 传染病研究 传染病研究
- 人类分子遗传学 人类分子遗传学
背景情况:
- 暴露于Mycobacterium结核病 (Mtb) 影响全球四分之一的人口,其中5-10%的人患结核病 (TB).
- 宿主遗传因素被假设有助于结核病疾病进展的变异性.
- 了解宿主基因对基因调节的影响对于识别结核病易感性和耐药性机制至关重要.
研究的目的:
- 研究宿主遗传变异与秘鲁人口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 (eQTLs) 及其与结核病进展状态的相互作用.
- 探索FAH基因和氨酸代谢在Mtb感染和结核病的背景下的作用.
主要方法:
- 结核病患者的家庭接触者的招募 (病例和对照).
- 对单细胞衍生的巨细胞和树突细胞 (DCs) 的转录组分析,以识别eQTLs.
- 对eQTL与结核病进展状况相互作用的分析.
- 在MTB感染细胞数据的分析以评估FAH基因调节和甲基化.
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中发现了与结核病进展状态相互作用的eQTL变异的四个基因.
- FAH基因与结核病进展有显著的eQTL相互作用,病例和对照之间的表达不同.
- 在公开数据集中,Mtb感染与FAH下调和DNA甲基化变化有关.
结论:
- 宿主基因变异显著影响免疫细胞中的基因表达,影响结核病风险.
- FAH基因和氨酸代谢途径代表了理解结核病原和进展的潜在目标.
- 这项研究强调了宿主遗传学,基因调节和传染病结果之间的相互作用.
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