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

IF 3.4 3区医学 Q2 INFECTIOUS DISEASES BMC Infectious Diseases Pub Date : 2024-10-16 DOI:10.1186/s12879-024-10073-0

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

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Abstract

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.

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伊朗重症 COVID-19 患者中 FCGR2A rs1801274 和 IL-6R rs2228145 多态性对托珠单抗反应的影响。

背景：尽管有报道称托西珠单抗（TCZ）对类风湿性关节炎的反应存在几种遗传生物标志物，但还没有研究涉及TCZ对COVID-19的药物基因组学影响：在这项前瞻性纵向研究中，选取了2020-2022年间的95名重症COVID-19患者。在服用TCZ前后的24小时、48小时和10天测量了患者的恢复过程。使用 RFLP-PCR 对所有参与者进行了基因分型。比较了FCGR2A rs1801274和IL-6R rs2228145的不同基因型对恢复过程的影响：43.2%的患者为男性，56.8%为女性，平均年龄为 58.20（± 16.214）岁。FCGR2A rs1801274 的 GA 基因型会增加 TCZ 治疗者的死亡风险（OR = 2.83，P = 0.038）和通气风险（OR = 2.71，P = 0.047）。然而，IL-6R rs2228145 不存在死亡和通气风险（P > 0.05）。此外，对接分析表明，不仅IL6R，FCGR2A也可以成为TCZ的配体：本研究就基因变异对COVID-19患者TCZ应答率的影响提供了有价值的见解。FCGR2A rs1801274的GA基因型与治疗效果不佳有关。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

BMC Infectious Diseases 医学-传染病学

CiteScore

6.50

自引率

0.00%

发文量

860

审稿时长

3.3 months

期刊介绍： BMC Infectious Diseases is an open access, peer-reviewed journal that considers articles on all aspects of the prevention, diagnosis and management of infectious and sexually transmitted diseases in humans, as well as related molecular genetics, pathophysiology, and epidemiology.