Polymorphisms in HLA genes among Brazilian patients hospitalized with COVID-19: Insights from a multicentric study.
СтатьяМногоцентровое исследованиеНазвание и аннотация: Перевод в очереди
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de Campos Martin Berber Gilcele, de Sarges Kevin Matheus Lima, da Cruz Thais Campos Dias, Roma Eric Henrique, Miyajima Fábio, Almeida Jorge Reis, de Souza Cíntia Fernandes, da Silva Andrea Alice, Vallinoto Izaura Maria Vieira Cayres, Vallinoto Antônio Carlos Rosário, Queiroz Maria Alice Freitas, Baccin Tatiana Gasperin, de Castro Andréa Cauduro, Vieira Angélica Thomaz, de Azevedo Francisco Kennedy Scoffoni, da Costa Pereira Alexandre, Falcão Luiz Fábio Magno, Quaresma Juarez Antônio Simões, Kehdy Fernanda, Santos Eduardo Tarazona, Siqueira Marilda Mendonça, Garcia Cristiana Couto, Dos Santos Eduardo José Melo, Slhessarenko Renata Dezengrini
Аннотация
Immunogenetic factors such as human leukocyte antigen (HLA) alleles, have yielded contrasting associations with protection or increased chances of hospitalization due to COVID-19 worldwide. This case-control study included 834 patients with confirmed COVID-19 diagnosis from five Brazilian states: Ceará (n = 110), Mato Grosso (n = 192), Pará (n = 209), Rio de Janeiro (n = 211) and Rio Grande do Sul (n = 112). Genotyping was performed using the Axiom™ Human Genotyping SARS-CoV-2 array, targeting single nucleotide polymorphisms in HLA class I and II genes; HLA alleles were imputed for eight loci. Among the 15 preselected candidate alleles, only DQA1∗05:01 (p = 0.015) in the state of Ceará remained significantly associated with hospitalization. The meta-analysis of the most frequent alleles in all states revealed that HLA-DPA1∗01:03 (p = 0.0229, OR = 0.76, 95 % CI = 0.60-0.96) and HLA-DPB1∗04:01 (p = 0.0474, OR = 0.78, 95 % CI = 0.611.00) were associated with protection against hospitalization, whereas HLA-DPA1∗02:01 (p = 0.0259, OR = 1.37, 95 % CI = 1.04-1.80), HLA-DQA1∗05:01 (p = 0.0133, OR = 1.40, 95 % CI = 1.07-1.82), and HLA-DRB1∗03:01 (p = 0.0276, OR: 1.59, 95 % CI: 1.05-2.40) associated with increased risk of hospitalization. HLA evolutionary divergence (HED) scores were significantly higher among the non-hospitalized group for the HLA-A locus, which has been shown to be a protective factor for the most severe forms and consequently hospitalization due to COVID-19.