Tuberculosis (TB) caused by Mycobacterium tuberculosis (M.tb) is a major health care threat worldwide causing over a million deaths annually. Host-pathogen interaction is complex, and a strong genetic contribution to disease susceptibility has been proposed. We have investigated single-nucleotide polymorphisms (SNPs) within cGAS/STING in Indian TB patients and healthy cohorts from India and Germany by Lightcycler®480 genotyping technique. The cGAS/STING pathway is an essential defense pathway within the cytosol after M.tb is internalized and mycobacterial DNA is released inducing the production of type I IFNs. We found that the rs311686 SNP upstream of cGAS provides protection from getting TB overall and is differently distributed in pulmonary TB patients compared with extra-pulmonary and particularly relapse cases. This SNP furthermore differs in distribution when comparing individuals with respect to BCG vaccination status. Taken together, our results show that the presence of the rs311686 SNP influences the course of TB significantly. However, structural conformation changes were found only for the cGAS rs610913 SNP. These findings underscore the importance of M.tb DNA recognition for TB pathogenesis and may eventually help in risk stratification of individuals. This may ultimately help in prevention of disease and aid in developing new vaccination and treatment strategies.

中文翻译：

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环状GMP-AMP合酶（cGAS）基因上游的SNP可防止复发和肺外结核病，并且与印度人群的BCG疫苗接种状况有关。

由结核分枝杆菌（M.tb）引起的结核病（TB）是世界范围内的主要医疗保健威胁，每年造成超过一百万的死亡。宿主-病原体相互作用是复杂的，并且已经提出了对疾病易感性的强大遗传贡献。我们已经通过Lightcycler®480基因分型技术研究了印度结核病患者以及印度和德国健康人群的cGAS / STING内的单核苷酸多态性（SNP）。在M.tb被内化并释放分枝杆菌DNA诱导I型IFN产生后，cGAS / STING途径是胞质溶胶中的必不可少的防御途径。我们发现，cGAS上游的rs311686 SNP可防止整体结核病的发生，与肺外和特别是复发病例相比，在肺结核患者中的分布有所不同。此外，在比较个人的BCG疫苗接种状况时，此SNP的分布也有所不同。两者合计，我们的结果表明，rs311686 SNP的存在显着影响结核病的病程。但是，仅在cGAS rs610913 SNP中发现了结构构象变化。这些发现强调了结核分枝杆菌的M.tb DNA识别的重要性，并可能最终有助于个体的风险分层。这最终可能有助于预防疾病，并有助于制定新的疫苗接种和治疗策略。这些发现强调了结核分枝杆菌的M.tb DNA识别的重要性，并可能最终有助于个体的风险分层。这最终可能有助于预防疾病，并有助于制定新的疫苗接种和治疗策略。这些发现强调了结核分枝杆菌的M.tb DNA识别的重要性，并可能最终有助于个体的风险分层。这最终可能有助于预防疾病，并有助于制定新的疫苗接种和治疗策略。