Genetic polymorphisms associated with susceptibility to COVID-19 disease and severity: A systematic review and meta-analysis

• Published in: PloS one Vol. 17; no. 7; p. e0270627
• Main Authors: Dieter, Cristine, Brondani, Letícia de Almeida, Leitão, Cristiane Bauermann, Gerchman, Fernando, Lemos, Natália Emerim, Crispim, Daisy
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 06.07.2022; Public Library of Science (PLoS)
• Subjects: Alleles; Analysis; Apolipoprotein E; Apolipoproteins E; Biology and Life Sciences; CCR5 protein; Comorbidity; Coronaviruses; COVID-19; COVID-19 - genetics; Disease susceptibility; Ethnicity; Evaluation; Gender; Gene polymorphism; Genetic aspects; Genetic diversity; Genetic polymorphisms; Genetic Predisposition to Disease; Genetic variance; Health risks; HLA-A Antigens; Humans; Medicine and Health Sciences; Meta-analysis; Mutation; Pathogenesis; Physical Sciences; Polymorphism; Polymorphism, Genetic; Research and Analysis Methods; Reviews; Severe acute respiratory syndrome coronavirus 2; Signs and symptoms; Systematic review; Viral diseases; Brazil
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0270627

Although advanced age and presence of comorbidities significantly impact the variation observed in the clinical symptoms of COVID-19, it has been suggested that genetic variants may also be involved in the disease. Thus, the aim of this study was to perform a systematic review with meta-analysis of the literature to identify genetic polymorphisms that are likely to contribute to COVID-19 pathogenesis. Pubmed, Embase and GWAS Catalog repositories were systematically searched to retrieve articles that investigated associations between polymorphisms and COVID-19. For polymorphisms analyzed in 3 or more studies, pooled OR with 95% CI were calculated using random or fixed effect models in the Stata Software. Sixty-four eligible articles were included in this review. In total, 8 polymorphisms in 7 candidate genes and 74 alleles of the HLA loci were analyzed in 3 or more studies. The HLA-A*30 and CCR5 rs333Del alleles were associated with protection against COVID-19 infection, while the APOE rs429358C allele was associated with risk for this disease. Regarding COVID-19 severity, the HLA-A*33, ACE1 Ins, and TMPRSS2 rs12329760T alleles were associated with protection against severe forms, while the HLA-B*38, HLA-C*6, and ApoE rs429358C alleles were associated with risk for severe forms of COVID-19. In conclusion, polymorphisms in the ApoE, ACE1, TMPRSS2, CCR5, and HLA loci appear to be involved in the susceptibility to and/or severity of COVID-19.