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Title: Alleles of HLA-DRB1∗04 associated with pulmonary tuberculosis in Amazon Brazilian population
Authors: Lima, Dhêmerson Souza de
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
Keywords: Early Secretory Antigenic Target 6
Hla Drb1 Antigen
Hla Drb1 Antigen
Hla-drb1*04 Antigen
Alcohol Consumption
Controlled Study
Correlation Analysis
Disease Transmission
Gene Frequency
Genetic Association
Genetic Susceptibility
Hla Drb1 Gene
Lung Tuberculosis
Major Clinical Study
Nucleotide Sequence
Polymerase Chain Reaction
Polymorphism, Genetic
Genetic Predisposition
Lung Tuberculosis
Middle Aged
Young Adult
Genetic Predisposition To Disease
Hla-drb1 Chains
Middle Aged
Polymorphism, Genetic
Tuberculosis, Pulmonary
Young Adult
Issue Date: 2016
metadata.dc.publisher.journal: PLoS ONE
metadata.dc.relation.ispartof: Volume 11, Número 2
Abstract: 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.
metadata.dc.identifier.doi: 10.1371/journal.pone.0147543
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