Genetic variability in COVID-19-related genes in the Brazilian population

Author(s):Show less -

Secolin, Rodrigo ^{[1, 2]} ; de Araujo, Tania K. ^{[1, 2]} ; Gonsales, Marina C. ^{[1, 2]} ; Rocha, Cristiane S. ^{[1, 2]} ; Naslavsky, Michel ^{[3, 4]} ; De Marco, Luiz ^[5] ; Bicalho, Maria A. C. ^[6] ; Vazquez, Vinicius L. ^[7] ; Zatz, Mayana ^{[3, 4]} ; Silva, Wilson A. ^[8] ; Lopes-Cendes, Iscia ^{[1, 2]}

Affiliation

^[1] Brazilian Inst Neurosci & Neurotechnol BRAINN, Campinas, SP - Brazil

^[2] Univ Campinas UNICAMP, Dept Translat Med, Campinas, SP - Brazil

^[3] Univ Sao Paulo, Inst Biosci, Dept Genet & Evolut Biol, USP, Sao Paulo, SP - Brazil

^[4] Human Genome & Stem Cell Res Ctr, Sao Paulo, SP - Brazil

^[5] Fed Univ Minas Gerais UFMG, Dept Surg, Belo Horizonte, MG - Brazil

^[6] Fed Univ Minas Gerais UFMG, Dept Clin Med, Belo Horizonte, MG - Brazil

^[7] Barretos Canc Hosp, Mol Oncol Res Ctr CPOM, Barretos, SP - Brazil

^[8] Univ Sao Paulo Ribeirao Preto USP, Ribeirao Preto Med Sch, Dept Genet, Ribeirao Preto, SP - Brazil

• Document type: Journal article
• Source: HUMAN GENOME VARIATION; v. 8, n. 1 APR 2 2021.
• Web of Science Citations: 2

Abstract

SARS-CoV-2 utilizes the angiotensin-converting enzyme 2 (ACE2) receptor and transmembrane serine protease (TMPRSS2) to infect human lung cells. Previous studies have suggested that different host ACE2 and TMPRSS2 genetic backgrounds might contribute to differences in the rate of SARS-CoV-2 infection or COVID-19 severity. Recent studies have also shown that variants in 15 genes related to type I interferon immunity to influenza virus might predispose patients toward life-threatening COVID-19 pneumonia. Other genes (SLC6A20, LZTFL1, CCR9, FYCO1, CXCR6, XCR1, IL6, CTSL, ABO, and FURIN) and HLA alleles have also been implicated in the response to infection with SARS-CoV-2. Currently, Brazil has recorded the third-highest number of COVID-19 cases worldwide. We aimed to investigate the genetic variation present in COVID-19-related genes in the Brazilian population. We analyzed 27 candidate genes and HLA alleles in 954 admixed Brazilian exomes. We used the information available in two public databases (http://www. bipmed.org and http://abraom.ib.usp.br/) and additional exomes from individuals born in southeast Brazil, the region of the country with the highest number of COVID-19 patients. Variant allele frequencies were compared with the 1000 Genomes Project phase 3 (1KGP) and gnomAD databases. We detected 395 nonsynonymous variants; of these, 325 were also found in the 1KGP and/or gnomAD. Six of these variants were previously reported to influence the rate of infection or clinical prognosis of COVID-19. The remaining 70 variants were identified exclusively in the Brazilian sample, with a mean allele frequency of 0.0025. In silico analysis revealed that seven of these variants are predicted to affect protein function. Furthermore, we identified HLA alleles previously associated with the COVID-19 response at loci DQB1 and DRB1. Our results showed genetic variability common to other populations and rare and ultrarare variants exclusively found in the Brazilian population. These findings might lead to differences in the rate of infection or response to infection by SARS-CoV-2 and should be further investigated in patients with this disease. (AU)

• FAPESP's process: 19/08526-8 - Ancestral genomic architecture evaluation in patients with focal and generalized epilepsy
• Grantee: Rodrigo Secolin
• Support Opportunities: Scholarships in Brazil - Technical Training Program - Technical Training
• FAPESP's process: 13/07559-3 - BRAINN - The Brazilian Institute of Neuroscience and Neurotechnology
• Grantee: Fernando Cendes
• Support Opportunities: Research Grants - Research, Innovation and Dissemination Centers - RIDC
• FAPESP's process: 17/01900-6 - Identification of the distribution of HLA alleles in the Brazilian population and in neurological phenotypes possibly associated with autoimmunity
• Grantee: Tânia Kawasaki de Araújo
• Support Opportunities: Scholarships in Brazil - Post-Doctoral