Lu Yanjun, Li Qian, Peng Jing, Zhu Yaowu, Wang Feng, Wang Chunyu, Wang Xiong
Department of Laboratory Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
Department of Stomatology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
Tuberculosis (Edinb). 2016 Mar;97:47-51. doi: 10.1016/j.tube.2016.01.001. Epub 2016 Jan 9.
The autophagy-related immunity-related GTPase family M protein, IRGM, plays an important role in the defense against tuberculosis (TB) infection. IRGM polymorphisms are associated with TB infection susceptibility, and recent studies demonstrate host genetic differences between active and latent TB. Here, we investigated the association between IRGM polymorphisms and TB infection type in a Chinese population. We recruited 268 and 321 patients with confirmed or latent TB, respectively, and 475 TB-free healthy controls. Three single nucleotide polymorphisms, rs10065172, rs10051924, and rs13361189 within IRGM were genotyped using TaqMan-based assays. Interferon-gamma release levels were tested by T-SPOT. rs10065172 (P = 0.024, OR 0.67 (95% CI 0.48-0.95)), rs10051924 (P = 0.01, OR 0.64 (95% CI 0.46-0.90)), and rs13361189 (P = 0.055, OR 0.72 (95% CI 0.51-1.01)) were associated with a protective role against latent TB progression. Haplotype analysis showed that TCC was protective for latent TB (P = 0.022, OR 0.74 (95% CI 0.57-0.96)) whereas TTC conferred a higher risk of active TB. Additionally, patients with the rs10065172 TT genotype had a higher response to TB specific antigens. Thus, IRGM polymorphism differences between latent and active TB suggests that genetic differences in autophagy might partly affect host TB infection status.
自噬相关免疫相关GTP酶家族M蛋白（IRGM）在抵御结核分枝杆菌（TB）感染中发挥重要作用。IRGM基因多态性与TB感染易感性相关，最近的研究表明活动性和潜伏性TB之间存在宿主遗传差异。在此，我们调查了中国人群中IRGM基因多态性与TB感染类型之间的关联。我们分别招募了268例确诊或潜伏性TB患者和321例潜伏性TB患者，以及475例无TB的健康对照。使用基于TaqMan的检测方法对IRGM基因内的三个单核苷酸多态性rs10065172、rs10051924和rs13361189进行基因分型。通过T-SPOT检测干扰素-γ释放水平。rs10065172（P = 0.024，OR 0.67（95%CI 0.48-0.95））、rs10051924（P = 0.01，OR 0.64（95%CI 0.46-0.90））和rs13361189（P = 0.055，OR 0.72（95%CI 0.51-1.01））与预防潜伏性TB进展的保护作用相关。单倍型分析表明，TCC对潜伏性TB具有保护作用（P = 0.022，OR 0.74（95%CI 0.57-0.96）），而TTC则增加了活动性TB的风险。此外，rs10065172 TT基因型患者对TB特异性抗原有更高的反应。因此，潜伏性和活动性TB之间的IRGM基因多态性差异表明，自噬的遗传差异可能部分影响宿主TB感染状态。
