在非洲儿童中与非伤寒型沙门氏菌病相关的遗传变异
James J Gilchrist1, Tara C Mills1, Vivek Naranbhai1
1Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK.
Lancet (London, England)
|August 28, 2015
概括
一种STAT4基因变异增加了非洲儿童对侵袭性非伤寒沙门氏菌 (NTS) 疾病的易感性. 这一发现为宿主遗传学和NTS感染提供了新的见解,有可能指导未来的控制策略.
科学领域:
- 遗传学
- 免疫学
- 传染性疾病
背景情况:
- 非伤寒型沙门氏菌 (NTS) 在非洲儿童中引起严重的,往往致命的侵袭性疾病.
- 目前的NTS预防,诊断和治疗策略不足.
- 主体遗传在NTS易感性中起作用,但在非洲人群中尚未研究.
研究的目的:
- 研究非洲儿童对侵入性NTS疾病的宿主遗传易感性.
- 确定与NTS风险相关的特定遗传变异.
- 探索已识别的变体对免疫反应的功能影响.
主要方法:
- 在肯尼亚儿童中进行全基因组关联研究 (GWAS),在马拉维儿童中进行复制.
- 在单细胞中分析表达量的特征位点 (eQTL),以评估变异性功能.
- 马拉维NTS病例中的血清干扰素 (IFNγ) 水平与基因型的相关性.
主要成果:
- 在肯尼亚和马拉维的儿童中,STAT4内基变异与NTS敏感性有显著的关联 (组合p=1. 4×10−9).
- 这种STAT4变体作为eQTL,NTS风险等位基因与IFNγ刺激单细胞中的STAT4表达率较低有关.
- 在马拉维儿童中,NTS风险基因与急性疾病期间的血清IFNγ度降低有关.
结论:
- STAT4是入侵性NTS疾病的高度可信的遗传易感基因.
- 鉴定到的STAT4变异影响IL12-IFNγ免疫轴,影响对NTS的敏感性.
- 这项研究提供了非洲儿童NTS疾病宿主遗传决定因素的第一个证据.
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