title: Alleles of HLA-DRB1*04 Associated with Pulmonary Tuberculosis in Amazon Brazilian Population.
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.
authors.affiliation: Programa de Pós-Graduação em Imunologia Básica e Aplicada, Instituto de Ciências Biológicas, Universidade Federal do Amazonas (UFAM), Manaus, Amazonas, Brasil.
authors.forename: Dhêmerson
authors.initials: D
authors.lastname: Souza de Lima
authors.affiliation: Laboratório de Micobacteriologia, Instituto Nacional de Pesquisas da Amazônia (INPA), Manaus, Amazonas, Brasil.
authors.forename: Mauricio
authors.initials: M
authors.lastname: Morishi Ogusku
authors.affiliation: Laboratório de Micobacteriologia, Instituto Nacional de Pesquisas da Amazônia (INPA), Manaus, Amazonas, Brasil.
authors.forename: Maisa
authors.initials: M
authors.lastname: Porto Dos Santos
authors.affiliation: Programa de Pós-Graduação em Ciências Farmacêuticas, Faculdade de Ciências Farmacêuticas (FCF), Manaus, Amazonas, Brasil.
authors.forename: Cláudia Maria
authors.initials: CM
authors.lastname: de Melo Silva
authors.affiliation: Programa de Pós-Graduação em Imunologia Básica e Aplicada, Instituto de Ciências Biológicas, Universidade Federal do Amazonas (UFAM), Manaus, Amazonas, Brasil.
authors.forename: Vanessa
authors.initials: V
authors.lastname: Alves de Almeida
authors.affiliation: Policlínica Cardoso Fontes, Manaus, Amazonas, Brasil.
authors.forename: Irineide
authors.initials: I
authors.lastname: Assumpção Antunes
authors.affiliation: Programa de Pós-Graduação em Imunologia Básica e Aplicada, Instituto de Ciências Biológicas, Universidade Federal do Amazonas (UFAM), Manaus, Amazonas, Brasil.
authors.forename: Antonio Luiz
authors.initials: AL
authors.lastname: Boechat
authors.affiliation: Programa de Pós-Graduação em Imunologia Básica e Aplicada, Instituto de Ciências Biológicas, Universidade Federal do Amazonas (UFAM), Manaus, Amazonas, Brasil.|Fundação de Medicina Tropical Doutor Heitor Vieira Dourado (FMT/HVD), Manaus, Amazonas, Brasil.|Universidade Nilton Lins, Manaus, Amazonas, Brasil.
authors.forename: Rajendranath
authors.initials: R
authors.lastname: Ramasawmy
authors.affiliation: Programa de Pós-Graduação em Imunologia Básica e Aplicada, Instituto de Ciências Biológicas, Universidade Federal do Amazonas (UFAM), Manaus, Amazonas, Brasil.
authors.forename: Aya
authors.initials: A
authors.lastname: Sadahiro
mesh_terms: D000328:Adult; D000483:Alleles; D001938:Brazil; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics; D059811:HLA-DRB1 Chains / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic / Q000235:genetics; D014397:Tuberculosis, Pulmonary / Q000235:genetics*; D055815:Young Adult
chemical_list: D059811:HLA-DRB1 Chains; C527195:HLA-DRB1*04 antigen