Alleles of HLA-DRB1∗04 associated with pulmonary tuberculosis in Amazon Brazilian population

• Autor(a) principal: Lima, Dhêmerson Souza de
• Data de Publicação: 2016
• Outros Autores: Ogusku, Maurício Morishi, Santos, Maria Cristina dos, Silva, Cláudia Maria de Melo, Almeida, Vanessa Alves de, Antunes, Irineide Assumpção, Boechat, Antonio Luiz, Ramasawmy, Rajendranath, Sadahiro, Aya
• Tipo de documento: Artigo
• Idioma: eng
• Título da fonte: Repositório Institucional do INPA
• Texto Completo: https://repositorio.inpa.gov.br/handle/1/14691
• topic: Early Secretory Antigenic Target 6; Hla Drb1 Antigen; Hla Drb1 Antigen; Hla-drb1*04 Antigen; Adult; Alcohol Consumption; Allele; Brasil; Brazilian; Controlled Study; Correlation Analysis; Disease Transmission; Female; Gender; Gene Frequency; Genetic Association; Genetic Susceptibility; Hla Drb1 Gene; Human; Lung Tuberculosis; Major Clinical Study; Male; Nucleotide Sequence; Polymerase Chain Reaction; Prevalence; Smoking; Allele; Polymorphism, Genetic; Genetic Predisposition; Genetics; Lung Tuberculosis; Middle Aged; Young Adult; Adult; Alleles; Brasil; Female; Genetic Predisposition To Disease; Hla-drb1 Chains; Humans; Male; Middle Aged; Polymorphism, Genetic; Tuberculosis, Pulmonary; Young Adult

Immunogenetic host factors are associated with susceptibility or protection to tuberculosis (TB). Strong associations of HLA class II genes with TB are reported. We analyzed the HLA-DRB1∗04 alleles to identify subtypes associated with pulmonary TB and their interaction with risk factors such as alcohol, smoking, and gender in 316 pulmonary TB patients and 306 healthy individuals from the Brazilian Amazon. The HLA-DRB1∗04 was prevalent in patients with pulmonary TB (p<0.0001; OR = 2.94; 95% CI = 2.12 to 4.08). Direct nucleotide sequencing of DRB1 exon 2 identified nine subtypes of HLA-DRB1∗04. The subtype HLA-DRB1∗04:11:01 (p = 0.0019; OR = 2.23; 95% CI = 1.34 to 3.70) was associated with susceptibility to pulmonary TB while DRB1∗04:07:01 (p<0.0001; OR = 0.02; 95% CI = 0.001 to 0.33) to protection. Notably, the interaction between alcohol and HLA-DRB1∗04:11:01 increased the risk for developing pulmonary TB (p = 0.0001; OR = 51.3; 95% CI = 6.81 to 386). Multibacillary pulmonary TB, the clinical presentation of disease transmission, was strongly associated with interaction to alcohol (p = 0.0026; OR = 11.1; 95% CI = 3.99 to 30.9), HLA-DRB1∗04:11:01 (p = 0.0442; OR =2.01; 95% CI = 1.03 to 3.93) and DRB1∗04:92 (p = 0.0112; OR = 8.62; 95% CI = 1.63 to 45.5). These results show that HLA-DRB1∗04 are associated with pulmonary TB. Interestingly, three subtypes, DRB1∗04:07:01, DRB1∗04:11:01 and DRB1∗04:92 of the HLA-DRB1∗04 could be potential immunogenetic markers that may help to explain mechanisms involved in disease development. © 2016 Souza de Lima et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.