Association of Polymorphisms of IL-6 Pathway Genes (IL6, IL6R and IL6ST) with COVID-19 Severity in an Amazonian Population.
Fabíola Brasil Barbosa RodriguesRosilene da SilvaErika Ferreira Dos SantosMioni Thieli Figueiredo Magalhães de BritoAndréa Luciana Soares da SilvaMauro de Meira LeiteFlávia Póvoa da CostaMaria de Nazaré do Socorro de Almeida VianaKevin Matheus Lima de SargesMarcos Henrique Damasceno CantanhedeAdriana de Oliveira Lameira VeríssimoMayara da Silva CarvalhoDaniele Freitas HenriquesCarla Pinheiro da SilvaIgor Brasil CostaJuliana Abreu Lima NunesIran Barros CostaGiselle Maria Rachid VianaMaria Alice Freitas QueirozSandra Souza LimaJeferson da Costa LopesMaria Karoliny da Silva TorresIzaura Maria Vieira Cayres VallinotoCarlos David Araújo BicharaAntonio Carlos Rosário VallinotoEduardo José Melo Dos SantosPublished in: Viruses (2023)
Interleukin-6 has been recognized as a major role player in COVID-19 severity, being an important regulator of the cytokine storm. Hence, the evaluation of the influence of polymorphisms in key genes of the IL-6 pathway, namely IL6, IL6R, and IL6ST, may provide valuable prognostic/predictive markers for COVID-19. The present cross-sectional study genotyped three SNPs (rs1800795, rs2228145, and rs7730934) at IL6. IL6R and IL6ST genes, respectively, in 227 COVID-19 patients (132 hospitalized and 95 non-hospitalized). Genotype frequencies were compared between these groups. As a control group, published data on gene and genotype frequencies were gathered from published studies before the pandemic started. Our major results point to an association of the IL6 C allele with COVID-19 severity. Moreover, IL-6 plasmatic levels were higher among IL6 CC genotype carriers. Additionally, the frequency of symptoms was higher at IL6 CC and IL6R CC genotypes. In conclusion, the data suggest an important role of IL6 C allele and IL6R CC genotype on COVID-19 severity, in agreement with indirect evidence from the literature about the association of these genotypes with mortality rates, pneumonia, and heightening of protein plasmatic levels pro-inflammatory driven effects.