Niu Hua, Wang Dong-Ping, Cai Xue-Qian, Fang Hao-Hui, Li Ye
Department of Respiratory and Critical Care Medicine, Anhui Chest Hospital, Hefei, China.
Department of Laboratory, Anhui Chest Hospital, Hefei, China.
BMC Infect Dis. 2025 Jul 22;25(1):933. doi: 10.1186/s12879-025-11288-5.
Studies have shown that autophagy was closely involved in host defense against mycobacteria, and genetic variations in autophagy genes were related to susceptibility to multiple diseases. We conducted this observational study to analyze the role of autophagy related genes polymorphisms and promoter methylation in the pathogenesis of pulmonary tuberculosis (PTB).
Ten single nucleotide polymorphisms (SNPs) in four autophagy related genes (ATG16L1, ATG5, IRGM, ULK1) were genotyped in 496 PTB patients and 498 controls using SNPscan technique, and the methylation levels of these genes were detected by MethylTarget technique in 98 PTB patients and 97 controls.
We found that ATG16L1 gene rs2241880 GG genotype frequency was significantly increased in PTB patients than that in controls. While, no significant association was found between PTB risk and ATG16L1 rs6754677, ATG5 rs2245214, rs510432, IRGM rs1000113, rs10065172, rs12658239, ULK1 rs7138581, rs9481, rs12297124. Haplotype analysis showed that ATG16L1 GA haplotype was associated with the increased risk to PTB, and ATG5 CC haplotype was related to the decreased risk to PTB. Stratification analysis demonstrated that ATG16L1 rs6754677, IRGM rs1000113, rs10065172 polymorphism were associated with pulmonary infection, and ULK1 rs7138581 polymorphism was related to fever, drug-induced liver injury in PTB patients. Compared with controls, ATG16L1 methylation level was significantly decreased in PTB, while ATG5, IRGM methylation levels were not significantly changed. Rs1000113, rs10065172, rs12658239 variants in IRGM had a major impact on IRGM methylation level in PTB patients.
ATG16L1, ATG5 genes variation and ATG16L1 gene methylation level were associated with the genetic background of PTB, while IRGM, ULK1 genes variations showed no significant association with PTB.
研究表明，自噬密切参与宿主对分枝杆菌的防御，自噬基因的遗传变异与多种疾病的易感性相关。我们开展这项观察性研究，以分析自噬相关基因多态性和启动子甲基化在肺结核（PTB）发病机制中的作用。
采用SNPscan技术对496例PTB患者和498例对照者的4个自噬相关基因（ATG16L1、ATG5、IRGM、ULK1）中的10个单核苷酸多态性（SNP）进行基因分型，采用MethylTarget技术在98例PTB患者和97例对照者中检测这些基因的甲基化水平。
我们发现，PTB患者中ATG16L1基因rs2241880的GG基因型频率显著高于对照者。然而，未发现PTB风险与ATG16L1 rs6754677、ATG5 rs2245214、rs510432、IRGM rs1000113、rs10065172、rs12658239、ULK1 rs7138581、rs9481、rs12297124之间存在显著关联。单倍型分析显示，ATG16L1的GA单倍型与PTB风险增加相关，ATG5的CC单倍型与PTB风险降低相关。分层分析表明，ATG16L1 rs6754677、IRGM rs1000113、rs10065172多态性与肺部感染相关，ULK1 rs7138581多态性与PTB患者的发热、药物性肝损伤相关。与对照者相比，PTB患者中ATG16L1的甲基化水平显著降低，而ATG5、IRGM的甲基化水平无显著变化。IRGM中的rs1000113、rs10065172、rs12658239变异对PTB患者的IRGM甲基化水平有重大影响。
ATG16L1、ATG5基因变异及ATG16L1基因甲基化水平与PTB的遗传背景相关，而IRGM、ULK1基因变异与PTB无显著关联。
