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Association of polymorphisms and abnormal methylation of several autophagy genes with pulmonary tuberculosis susceptibility, clinical manifestations in a Chinese population
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Association of polymorphisms and abnormal methylation of several autophagy genes with pulmonary tuberculosis susceptibility, clinical manifestations in a Chinese population
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Journal Article
Association of polymorphisms and abnormal methylation of several autophagy genes with pulmonary tuberculosis susceptibility, clinical manifestations in a Chinese population
2025
Overview
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.
Publisher
BioMed Central,BioMed Central Ltd,Springer Nature B.V,BMC
Subject
/ Autophagy-Related Protein 5 - genetics
/ Autophagy-Related Protein-1 Homolog - genetics
/ Autophagy-Related Proteins - genetics
/ China
/ Female
/ Genes
/ Genetic Predisposition to Disease
/ Genotype
/ GTP-Binding Proteins - genetics
/ Humans
/ Infectious disease and antibiotic resistance epidemiology
/ Intracellular Signaling Peptides and Proteins
/ Male
/ Medicine
/ Polymorphism, Single Nucleotide
/ Single nucleotide polymorphisms
