Impacto de variantes no gene MTOR na gravidade da COVID-19 em uma população brasileira

Abstract

Introduction: SARS-CoV-2’s pandemic has caused thousands of deaths worldwide. The disease’s severity is associated with age, sex, ongoing comorbidities along with exacerbated and uncontrolled systemic inflammatory response resulting from cytokine storm. Cytokine storms are characterized by a large dysregulated release of cytokines that can be triggered by viral infections and modulated by various signaling pathways. The target protein of rapamycin in mammals (mTOR) is a serine threonine kinase capable of shaping cellular activation and inflammatory innate response of cells, which is the first line of defense against viruses. The mTORC1 pathway has been shown to be affected by SARS-CoV-2 and hyperactivated in COVID-19’s severe patients which suggest that dysregulation of this pathway might play an important role in poor prognosis of disease. In addition, the genetic background of patients could possibly contribute to this outcome. Objectives: To investigate the involvement of variants in the MTOR gene with the severity of COVID-19 in the Brazilian population. Methods: Individuals with severe and mild COVID-19 were recruited and peripheral blood samples and sociodemographic data were collected. The SNVs rs1057079 and rs2536 of the MTOR gene were genotyped by RT-qPCR. We performed logistic regression analysis and Kaplan-Meier survival curves. We applied a genetic risk score to estimate the cumulative contribution of risk alleles. Plasma levels of the cytokines TNF and IL-6 were measured by ELISA and analyzed. Results and Conclusions: The T allele of rs1057079 was associated with risk of severity and critical COVID-19, as well as increased plasma levels of TNF. Meanwhile, the TT genotype of rs2536 was associated with death from COVID-19. The variant risk alleles showed a cumulative risk when inherited together and may be useful in predicting a more severe outcome of COVID-19.