Genetic variability in COVID-19-related genes in the Brazilian population
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Universidade Federal de Minas Gerais
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Artigo de periódico
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Membros da banca
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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.
Abstract
Assunto
COVID-19, Pneumonia, (Brasil)
Palavras-chave
COVID-19, Brazilian, Genes
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https://www.nature.com/articles/s41439-021-00146-w