title: Do HLA class II genes protect against pulmonary tuberculosis? A systematic review and meta-analysis.
abstract: Pulmonary tuberculosis (PTB) develops by a complex combination of environmental, immunological and socioeconomic factors and genetic susceptibility. The human leukocyte antigen (HLA) is the most polymorphic biological system and plays an essential role in the immune response against PTB. The aim of this study was to carry out a systematic review and meta-analysis evaluating the relationship between HLA-DRB1, HLA-DQB1 and HLA-DQA1 gene polymorphisms as possible risk or protective factors for PTB. A systematic search of the PubMed and Scopus databases was conducted following the guidelines described in the PRISMA statement. Fifty-six alleles were included in the meta-analysis. In the total pooled results, HLA-DRB1*08:03 (OR 1.95, CI 1.29-2.96), HLA-DQB1*06:01 (OR 1.78, CI 1.39-2.28), HLA-DQB1*06:09 (OR 2.27, 95 % CI 1.04-4.96) and HLA-DQA1*01:01 (OR 2.12, CI 1.11-4.03) genes were related to higher susceptibility to PTB. Conversely, the presence of the genes HLA-DRB1*07:01 (OR 0.74, CI 0.56-0.97), HLA-DQB1*03:01 (OR 0.77, CI 0.61-0.97), HLA-DQB1*04:02 (OR 0.57, CI 0.39-0.83), HLA-DQA1*04:01 (OR 0.50, CI 0.26-0.95) and HLA-DQA1*05:01 (OR 0.66, CI 0.48-0.92) demonstrated protection against PTB. In an analysis by ethnic subgroups, we found more genetic associations in Caucasians than in Asians. These findings suggest that HLAs may be used as markers for acquisition and development of PTB. To strengthen PTB susceptibility/resistance, we recommend further multicentric studies in different geographic regions, with certainty of controls' exposure to M. tuberculosis by use of marker of latent or active PTB, with analysis stratified by ethnic groups, with descriptions of specific alleles and carrying out immunological functionality tests.
authors.affiliation: Graduate Program in Health Sciences, Federal University São João Del-Rei, 400 Sebastião Gonçalves Coelho Avenue, Divinópolis, MG, 35501-296, Brazil.
authors.forename: A
authors.initials: A
authors.lastname: Oliveira-Cortez
authors.affiliation: Research Core in Epidemiology and Public Health, Federal University São João Del-Rei, 400 Sebastião Gonçalves Coelho Avenue, Divinópolis, MG, 35501-296, Brazil.
authors.forename: A C
authors.initials: AC
authors.lastname: Melo
authors.affiliation: Laboratory of Physiology, Federal University São João Del-Rei, 400 Sebastião Gonçalves Coelho Avenue, Divinópolis, MG, 35501-296, Brazil.
authors.forename: V E
authors.initials: VE
authors.lastname: Chaves
authors.affiliation: Institute of Biomedical Sciences, Department of Immunology, University of São Paulo, 1730 Lineu Prestes Avenue, São Paulo, SP, 05508-000, Brazil.
authors.forename: A
authors.initials: A
authors.lastname: Condino-Neto
authors.affiliation: Graduate Program in Health Sciences, Federal University São João Del-Rei, 400 Sebastião Gonçalves Coelho Avenue, Divinópolis, MG, 35501-296, Brazil. paulo.camargos@pq.cnpq.br.
authors.forename: P
authors.initials: P
authors.lastname: Camargos
mesh_terms: D044466:Asian People; D005787:Gene Frequency; D005802:Genes, MHC Class II; D020022:Genetic Predisposition to Disease; D006801:Humans; D009169:Mycobacterium tuberculosis / Q000276:immunology*; D010750:Phosphoproteins / Q000235:genetics*; D014397:Tuberculosis, Pulmonary / Q000235:genetics* / Q000276:immunology; D044465:White People
chemical_list: C574674:La protein, human; D010750:Phosphoproteins