Alleles of HLA-DRB104 Associated with Pulmonary Tuberculosis in Amazon Brazilian Population

• Published in: PloS one Vol. 11; no. 2; p. e0147543
• Main Authors: Souza de Lima, Dhêmerson, Morishi Ogusku, Mauricio, Porto Dos Santos, Maisa, de Melo Silva, Cláudia Maria, Alves de Almeida, Vanessa, Assumpção Antunes, Irineide, Boechat, Antonio Luiz, Ramasawmy, Rajendranath, Sadahiro, Aya
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 22-02-2016; Public Library of Science (PLoS)
• Subjects: Adult; Alcohol; Alcohol use; Alcohols; Alleles; Antigens; Biology and Life Sciences; Brazil; Deoxyribonucleic acid; Diabetes; Disease; Disease transmission; DNA; Drb1 protein; Female; Genetic Predisposition to Disease - genetics; Histocompatibility antigen HLA; HLA-DRB1 Chains - genetics; Humans; Immunogenetics; Immunology; Male; Medicine and Health Sciences; Middle Aged; Patients; People and places; Polymorphism, Genetic - genetics; Population; Research and Analysis Methods; Rheumatoid arthritis; Risk analysis; Risk factors; Smoking; Social Sciences; Studies; Tuberculosis; Tuberculosis, Pulmonary - genetics; Young Adult; Brazil
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0147543

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.