Association between single-nucleotide polymorphism rs868875 of CLEC4M gene and clinical severity of COVID-19 in a Brazilian population.

COVID-19, caused by the SARS-CoV-2 virus, has had a global impact, leading to high incidence and mortality rates worldwide. Host genetics significantly influence individual susceptibility to severe COVID-19. The C-type lectin domain family 4 member M (CLEC4M) gene plays an important role in SARS-CoV-2 infection and coagulation pathways. In this study, we genotyped and investigated the functional variant rs868875 of the CLEC4M gene in COVID-19 patients receiving anticoagulant therapy. This cross-sectional study included 485 patients, divided into moderate (n = 139) and critical/severe (n = 346) groups. Significant disparities in D-dimer levels were observed between patient groups (p < 0.0001), thus serving as a critical marker for stratification. Genetic analysis revealed significant associations between allele (p = 0.0170) and genotype (p = 0.0096) frequencies across the groups. Regarding genotypic models, an association was found in dominant (p = 0.0035) and overdominant (p = 0.004) models. Logistic regression confirmed that the presence of G allele (AG/GG) significantly impacts COVID-19 severity, independent of confounding variables (p = 0.017). Moreover, expression quantitative trait loci (eQTLs) analysis indicated that the GG genotype of rs868875 is associated with lower CLEC4M gene expression in lung and liver tissue, and STRING analysis revealed relevant biological interactions between CLEC4M and other genes in the inflammatory process, innate immunity, and vascular response. Overall, our findings suggest an association between the rs868875 polymorphism and severe clinical outcomes of COVID-19 in patients receiving anticoagulants. However, further validation studies are essential to corroborate these findings and elucidate the functional implications of this polymorphism. These efforts will contribute to a comprehensive understanding of the pathogenesis of COVID-19.