Impact of FCGR2A rs1801274 and IL-6R rs2228145 polymorphisms on tocilizumab response in the Iranian population with severe COVID-19

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2024年10月16日

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Nastaran Injinari,
Samira Asadollahi,
Fateme Sefid,
Maedeh Arshadi,
Saeedeh Sadat Hosseini,
Hamed Ghoshouni,
Fatemeh Soltani,
Nasim Namiranian,
Mohammad Hasan Sheikhha,
Fatemeh Aghaeimeybodi

摘要

Background

Although several genetic biomarkers have been reported in the tocilizumab (TCZ) response in rheumatoid arthritis, no studies have addressed the pharmacogenomics effect of TCZ in COVID-19.

Methods

In this prospective longitudinal study, 95 individuals with severe COVID-19 were selected between 2020–2022. The recovery process was measured at 24 h, 48 h, and 10 days before and after taking TCZ. All participants were genotyped using RFLP-PCR. Different genotypes of FCGR2A rs1801274 and IL-6R rs2228145 were compared in terms of the recovery process.

Results

43.2% of patients were male and 56.8% were female with an average age of 58.20(± 16.214) years. The GA genotype for FCGR2A rs1801274 increased the risk of death (OR = 2.83, P = 0.038) and ventilation (OR = 2.71, P = 0.047) in TCZ-treated individuals. However, there was no risk of death and ventilation with IL-6R rs2228145 (P > 0.05). Additionally, docking analysis showed that not only IL6R but also FCGR2A can be a ligand for TCZ.

Conclusion

This study provides valuable insights into the impact of genetic variations on the response rate of TCZ in COVID-19 patients. The GA genotype for FCGR2A rs1801274 was associated with poor treatment outcomes.