CTLA-4 rs5742909 but not ADAM33 rs2280091 is a predictor factor for COVID-19 mortality

Background: Research has demonstrated the association between susceptibility to coronavirus disease 2019 (COVID-19) and single nucleotide polymorphisms (SNPs). On the other hand, the cytotoxic T lymphocyte- associated antigen-4 (CTLA-4) serves as a pivotal inhibitory receptor with a substantial impact on the advancement of viral infections. Besides, the disintegrin and metalloproteinase33 ( ADAM33 ) gene is associated with both asthma and heightened airway responsiveness. Hence, this investigation sought to elucidate the potential association between the CTLA-4 rs5742909 and ADAM33 rs2280091 SNPs and the fatality rate of COVID-19 across various variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Methods: Both SNPs were genotyped with the PCR-RFLP assay in 1734 improved and 1450 deceased individuals. Results: Our obtained results revealed a significant association between the CTLA-4 rs5742909 C/T-T/T genotypes and increased mortality risk of COVID-19 in three different SARS-CoV-2 variants. The ADAM33 rs2280091 polymorphism demonstrated no significant association with COVID-19 mortality under various inheritance models. Nevertheless, subsequent adjustments for SARS-CoV-2 variants revealed a notable association between the GA genotype of ADAM33 rs2280091 and mortality rates specifically among individuals infected with the Delta variant. Conclusions: In summary, the prediction of COVID-19 severity could be facilitated through the utilization of the CTLA-4 rs5742909 marker. Conversely, in the case of ADAM33 rs2280091, such prognostication appears to be contingent upon the specific variants of the SARS-CoV-2 virus. (c) 2024 The Author(s). Published by Elsevier Ltd on behalf of King Saud Bin Abdulaziz University for Health Sciences. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/ 4.0/).