Association of polymorphisms and abnormal methylation of several autophagy genes with pulmonary tuberculosis susceptibility, clinical manifestations in a Chinese population
Abstract Background 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 polymor...
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BMC
2025-07-01
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| Series: | BMC Infectious Diseases |
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| Online Access: | https://doi.org/10.1186/s12879-025-11288-5 |
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| author | Hua Niu Dong-Ping Wang Xue-Qian Cai Hao-Hui Fang Ye Li |
| author_facet | Hua Niu Dong-Ping Wang Xue-Qian Cai Hao-Hui Fang Ye Li |
| author_sort | Hua Niu |
| collection | DOAJ |
| description | Abstract Background 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). Methods 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. Results 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. Conclusion 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. |
| format | Article |
| id | doaj-art-edc5898e794049d897b8bc1f78db9d61 |
| institution | Kabale University |
| issn | 1471-2334 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Infectious Diseases |
| spelling | doaj-art-edc5898e794049d897b8bc1f78db9d612025-08-20T03:45:47ZengBMCBMC Infectious Diseases1471-23342025-07-0125111310.1186/s12879-025-11288-5Association of polymorphisms and abnormal methylation of several autophagy genes with pulmonary tuberculosis susceptibility, clinical manifestations in a Chinese populationHua Niu0Dong-Ping Wang1Xue-Qian Cai2Hao-Hui Fang3Ye Li4Department of Respiratory and Critical Care Medicine, Anhui Chest HospitalDepartment of Laboratory, Anhui Chest HospitalDepartment of Respiratory and Critical Care Medicine, Anhui Chest HospitalDepartment of Respiratory and Critical Care Medicine, Anhui Chest HospitalDepartment of Tuberculosis, Anhui Chest HospitalAbstract Background 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). Methods 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. Results 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. Conclusion 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.https://doi.org/10.1186/s12879-025-11288-5Pulmonary tuberculosisSingle nucleotide polymorphismsDNA methylationAutophagy |
| spellingShingle | Hua Niu Dong-Ping Wang Xue-Qian Cai Hao-Hui Fang Ye Li Association of polymorphisms and abnormal methylation of several autophagy genes with pulmonary tuberculosis susceptibility, clinical manifestations in a Chinese population BMC Infectious Diseases Pulmonary tuberculosis Single nucleotide polymorphisms DNA methylation Autophagy |
| title | Association of polymorphisms and abnormal methylation of several autophagy genes with pulmonary tuberculosis susceptibility, clinical manifestations in a Chinese population |
| title_full | Association of polymorphisms and abnormal methylation of several autophagy genes with pulmonary tuberculosis susceptibility, clinical manifestations in a Chinese population |
| title_fullStr | Association of polymorphisms and abnormal methylation of several autophagy genes with pulmonary tuberculosis susceptibility, clinical manifestations in a Chinese population |
| title_full_unstemmed | Association of polymorphisms and abnormal methylation of several autophagy genes with pulmonary tuberculosis susceptibility, clinical manifestations in a Chinese population |
| title_short | Association of polymorphisms and abnormal methylation of several autophagy genes with pulmonary tuberculosis susceptibility, clinical manifestations in a Chinese population |
| title_sort | association of polymorphisms and abnormal methylation of several autophagy genes with pulmonary tuberculosis susceptibility clinical manifestations in a chinese population |
| topic | Pulmonary tuberculosis Single nucleotide polymorphisms DNA methylation Autophagy |
| url | https://doi.org/10.1186/s12879-025-11288-5 |
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