Cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) +49A>G (rs231775) gene polymorphism is not associated with COVID-19 severity and mortality in an Iranian population

Ensie Sadat Mirsharif; Abdolrahman Rostamian; Mohammadreza Salehi; Nayere Askari; Tooba Ghazanfari

doi:10.1016/j.heliyon.2023.e23308

Cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) +49A>G (rs231775) gene polymorphism is not associated with COVID-19 severity and mortality in an Iranian population

Heliyon. 2023 Dec 8;10(1):e23308. doi: 10.1016/j.heliyon.2023.e23308. eCollection 2024 Jan 15.

Authors

Ensie Sadat Mirsharif¹, Abdolrahman Rostamian², Mohammadreza Salehi³, Nayere Askari^{1

4}, Tooba Ghazanfari¹

Affiliations

¹ Immunoregulation Research Center, Shahed University, Tehran, Iran.
² Rheumatology Research Center, Imam Khomeini Hospital, Tehran University of Medical Sciences, Tehran, Iran.
³ Department of Infectious and Tropical Medicines, Tehran University of Medical Sciences, Tehran, Iran.
⁴ Department of Biology, Faculty of Basic Sciences, Shahid Bahonar, University of Kerman, Kerman, Iran.

Abstract

Introduction: Cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) regulates T cell immune responses as an immune activation inhibitor. Literature reviews suggest that COVID-19 is associated with dysregulation of the inflammatory immune response. The purpose of the present hospital-based case-control study was to evaluate the genetic association of the CTLA4 +49A > G (rs231775) Single Nucleotide Polymorphism (SNP) with COVID-19 severity and mortality among the Iranian people.

Method: Genomic DNA of peripheral blood nuclear cells was extracted from the 794 COVID-19 patients and 167 control individuals. The polymorphic site of rs231775 was genotyped using the PCR-RFLP technique. Also, to identify whether this genetic variation was related to CTLA-4 mRNA expression, total RNA was extracted from 178 COVID-19 patients and 70 controls. The mRNA levels of CTLA-4 were determined using real-time PCR.

Result: There were no statistically significant differences found in the genotype and allele frequencies among the different genetic models with regards to the severity and mortality of COVID-19. Furthermore, there was no significant association between rs231775 genotypes and CTLA-4 mRNA expression in patients.

Conclusion: Our findings demonstrated that SARS-CoV-2 infection is not associated with rs231775 in the Iranian people. More investigations are crucial to show how this genetic variation affects other ethnic groups. Given the importance of CTLA-4 in regulating immune responses, further studies are recommended to examine other CTLA-4 SNPs and the function of this gene in COVID-19 patients.

Keywords: COVID-19; CTLA-4; Polymorphism.