Department of Medicine, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands.
PLoS One. 2012;7(8):e41618. doi: 10.1371/journal.pone.0041618. Epub 2012 Aug 6.
Recent data suggest that autophagy is important for intracellular killing of Mycobacterium tuberculosis, and polymorphisms in the autophagy gene IRGM have been linked with susceptibility to tuberculosis (TB) among African-Americans, and with TB caused by particular M. tuberculosis genotypes in Ghana. We compared 22 polymorphisms of 14 autophagy genes between 1022 Indonesian TB patients and 952 matched controls, and between patients infected with different M. tuberculosis genotypes, as determined by spoligotyping. The same autophagy polymorphisms were studied in correlation with ex-vivo production of TNF, IL-1β, IL-6, IL-8, IFN-γ and IL-17 in healthy volunteers. No association was found between TB and polymorphisms in the genes ATG10, ATG16L2, ATG2B, ATG5, ATG9B, IRGM, LAMP1, LAMP3, P2RX7, WIPI1, MTOR and ATG4C. Associations were found between polymorphisms in LAMP1 (p = 0.02) and MTOR (p = 0.02) and infection with the successful M. tuberculosis Beijing genotype. The polymorphisms examined were not associated with M. tuberculosis induced cytokines, except for a polymorphism in ATG10, which was linked with IL-8 production (p = 0.04). All associations found lost statistical significance after correction for multiple testing. This first examination of a broad set of polymorphisms in autophagy genes fails to show a clear association with TB, with M. tuberculosis Beijing genotype infection or with ex-vivo pro-inflammatory cytokine production.
最近的数据表明自噬对于结核分枝杆菌的细胞内杀伤很重要，自噬基因 IRGM 的多态性与非裔美国人的结核病易感性有关，也与加纳特定结核分枝杆菌基因型引起的结核病有关。我们比较了 14 个自噬基因中的 22 个多态性在 1022 名印度尼西亚结核病患者和 952 名匹配对照之间，以及在根据 spoligotyping 确定的不同结核分枝杆菌基因型感染的患者之间。在健康志愿者中，我们研究了相同的自噬多态性与 TNF、IL-1β、IL-6、IL-8、IFN-γ和 IL-17 的体外产生之间的相关性。在基因 ATG10、ATG16L2、ATG2B、ATG5、ATG9B、IRGM、LAMP1、LAMP3、P2RX7、WIPI1、MTOR 和 ATG4C 中，未发现多态性与结核病之间存在关联。在 LAMP1（p = 0.02）和 MTOR（p = 0.02）多态性与成功的结核分枝杆菌北京基因型感染之间存在关联。除了 ATG10 中的一个多态性与 IL-8 产生有关（p = 0.04）外，所检查的多态性与 M. tuberculosis 诱导的细胞因子无关。所有关联在进行多次测试校正后均失去统计学意义。这是首次对广泛的自噬基因多态性进行检查，未显示与结核病、结核分枝杆菌北京基因型感染或体外促炎细胞因子产生有明显关联。
