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Relatedness and HLA-DRB1 typing may discriminate the magnitude of the genetic susceptibility to tuberculosis using a household contact model
  1. N Lucena-Silva1,2,
  2. M D Baliza1,3,
  3. A E S Martins2,
  4. N H S Deghaide4,
  5. K M Teixeira1,
  6. L C Rodrigues5,
  7. R Ximenes6,7,
  8. E A Donadi4,
  9. M d F P M de Albuquerque1,8
  1. 1Centro de Pesquisas Aggeu Magalhães, Fundação Oswaldo Cruz. Av. Moraes Rego, S/N, Campus da UFPE, Recife, PE, Brazil
  2. 2Serviço de Oncologia Pediátrica, Instituto de Medicina Integral Professor Fernando Figueira, Rua dos Coelhos, Boa Vista, Recife, PE, Brazil
  3. 3Centro de Ciências da Saúde, Universidade Federal do Recôncavo da Bahia, Santo Antônio de Jesus, BA, Brazil
  4. 4Depto. de Imunologia Clínica, Faculdade de Medicina de Ribeirão Preto,Universidade de São Paulo, Av. Bandeirantes, Monte Alegre, Ribeirão Preto, SP, Brazil
  5. 5Dept. of Epidemiology of the London School of Hygiene Tropical Medicine, London, UK
  6. 6Depto. de Medicina Tropical e, Av. Moraes Rego, S/N, Bl.A. Térreo do Hospital das Clínicas da UFPE, Cidade Universitária, Recife, PE, Brazil
  7. 7Depto. de Medicina Interna da Universidade Estadual de Pernambuco, Rua Arnóbio Marques, Santo Amaro, Recife, PE, Brazil
  8. 8Depto. de Medicina Interna da Universidade Federal de Pernambuco, Av. Moraes Rego, S/N, Bl.A. Térreo do Hospital das Clínicas da UFPE, Cidade Universitária, Recife, PE, Brazil
  1. Correspondence to Norma Lucena-Silva, Centro de Pesquisas Aggeu Magalhães, Fundação Oswaldo Cruz. Av. Moraes Rego, S/N, Cidade Universitária, Recife, PE, cep.: 50670-420, Brazil; norma.lucena{at}hotmail.com

Abstract

Background Tuberculosis clusters in families may be due to increased household exposure, shared genetic factors, or both. Household contact studies are useful to control exposure because socioeconomic and environmental conditions are similar to all subjects, allowing the evaluation of the contribution of relatedness to disease development.

Methods In this study, the familial aggregation of tuberculosis using relatedness and a specific inherited marker (HLA-DRB1) was evaluated. Fifty families, which had at least two cases of tuberculosis diagnosed within the past 5 years, were selected from a cohort of tuberculosis carried out in Recife, Brazil. The first case diagnosed was considered to be a primary case. The secondary attack rate of tuberculosis in household contacts was estimated according to the degree of relatedness. The relative risk of having tuberculosis based on the degree of relatedness household and the population attributable fraction to relatedness were also estimated. HLA-DRB1 typing and attributable etiologic/preventive fractions were calculated among sick and healthy household contacts.

Results Compared to unrelated contacts, the relative risk for tuberculosis adjusted for age was 1.38 (95% CI 0.86 to 2.21). Relatedness contributed 23% to the development of tuberculosis at the population levels. The HLA-DRB1*04 allele group (OR=2.44; p=0.0324; etiologic fraction=0.15) was overrepresented and the DRB1*15 allele group (OR=0.48; p=0.0488; protective fraction=0.19) was underrepresented among household contacts exhibiting tuberculosis. The presence of DRB1 shared alleles between primary cases and their contacts was a risk factor for tuberculosis (p=0.0281).

Conclusion This household contact model together with the utilisation of two genetic variables permitted the evaluation of genetic factors contributing towards tuberculosis development.

  • Tuberculosis
  • transmission
  • risk of tuberculosis
  • household contact
  • pedigree analysis

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Footnotes

  • Funding CNPq (Brazilian Council for Scientific and Technological Development).

  • Competing interests None.

  • Ethics approval This study was conducted with the approval of the Ethical Committee of the Aggeu Magalhães Research Center/Oswaldo Cruz Foundation of the Brazilian Health Ministry.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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