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CN 34-1304/RISSN 1674-3679

Volume 29 Issue 2
Feb.  2025
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LI Yue, MA Shuo, LIU Yue, TANG Qinyan, GUO Yu, LIU Yang, PEI Shengfei, FENG Fumin. Study on the relationship between TLR2 and TLR4 polymorphism and CpG island methylation and anti-tuberculosis drug-induced liver injury[J]. CHINESE JOURNAL OF DISEASE CONTROL & PREVENTION, 2025, 29(2): 217-223. doi: 10.16462/j.cnki.zhjbkz.2025.02.015
Citation: LI Yue, MA Shuo, LIU Yue, TANG Qinyan, GUO Yu, LIU Yang, PEI Shengfei, FENG Fumin. Study on the relationship between TLR2 and TLR4 polymorphism and CpG island methylation and anti-tuberculosis drug-induced liver injury[J]. CHINESE JOURNAL OF DISEASE CONTROL & PREVENTION, 2025, 29(2): 217-223. doi: 10.16462/j.cnki.zhjbkz.2025.02.015

Study on the relationship between TLR2 and TLR4 polymorphism and CpG island methylation and anti-tuberculosis drug-induced liver injury

doi: 10.16462/j.cnki.zhjbkz.2025.02.015
Funds:

National Natural Science Foundation of China 81041096

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  • Corresponding author: FENG Fumin, E-mail: fm_feng@sina.com
  • Received Date: 2023-11-20
  • Rev Recd Date: 2024-04-09
  • Available Online: 2025-03-08
  • Publish Date: 2025-02-10
  •   Objective  To investigate the relationship between single nucleotide polymorphisms rs7656411, rs3804099, rs1927914, rs1927911 in Toll-like receptor 2 (TLR2) and Toll-like receptor 4 (TLR4) genes, as well as CpG island methylation in the TLR2 gene promoter region, and anti-tuberculosis drug-induced liver injury (ADLI).  Methods  From July 2019 to March 2022, 322 tuberculosis patients with ADLI and 322 tuberculosis patients without ADLI were selected and matched 1∶1 based on gender, age, and treatment regimen. Gene polymorphisms and methylation patterns were detected using methylation-specific polymerase chain reaction(PCR) and PCR-restriction fragment length polymorphism(PCR-RFLP) technique.  Results  The wild-type genotype of TLR2 gene rs3804099 site (OR=0.55, 95% CI: 0.31-0.96) and CpG island methylation rate (OR=1.81, 95% CI: 1.07-3.06) were significantly higher in ADLI patients than in the control group (P < 0.05), with no statistical difference in the genotype frequency of other polymorphic sites between the two groups. Multivariate analysis showed that the wild-type TT of TLR2 gene rs3804099 site was associated with the progression of ADLI, and the wild-type TT may be a protective factor for ADLI OR=0.53 (95% CI: 0.38-0.75). In addition, high methylation of CpG island in TLR2 gene was independently associated with the risk of ADLI, with adjusted OR of 1.86 (95% CI: 1.05-3.28). The interaction between the mutation of rs3804099 site and high methylation of CpG island increased the risk of ADLI, being 2.12 times that of the control group (OR=2.12, 95% CI: 1.36-3.29).  Conclusions  There is an association between TLR2 gene polymorphism and CpG island methylation and ADLI. The interaction between CpG island methylation in the TLR2 gene promoter region and the gene polymorphism at rs3804099 is associated with a high risk of ADLI.
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