Observational studyBMC infectious diseases2025
Association of polymorphisms and abnormal methylation of several autophagy genes with pulmonary tuberculosis susceptibility, clinical manifestations in a Chinese population.
Observational study in BMC infectious diseases, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Not yet cited in PubMed.
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Abstract
backgroundStudies 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).
methodsTen 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.
resultsWe 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.
conclusionATG16L1, 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.
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