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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. Norma Lucena-Silva1,
  2. Marcilio D Baliza2,
  3. Albert Eduardo Silva Martins3,
  4. Neife Hassam Saloum Deghaide4,
  5. Kirte M Teixeira5,
  6. Laura C Rodrigues6,
  7. Ricardo Ximenes7,
  8. Eduardo Antônio Donadi4,
  9. Maria de Fátima P M de Albuquerque1
  1. 1 Centro de Pesquisas Aggeu Magalhães/Fiocruz e Faculdade de Medicina da UFPE, Brazil;
  2. 2 Centro de Ciências da Saúde, Universidade Federal do Recôncavo da Bahia, Brazil;
  3. 3 Serviço de Oncologia Pediátrica, Instituto de Medicina Integral Professor Fernando Fig, Brazil;
  4. 4 Depto. de Imunologia Clínica, Faculdade de Medicina de Ribeirão Preto,Universidade de, Brazil;
  5. 5 Centro de Pesquisas Aggeu Magalhães/Fiocruz, Brazil;
  6. 6 Dept. of Epidemiology, London School of Hygiene and Tropical Medicine, United Kingdom;
  7. 7 Depto. de Medicina Tropical e 8Depto. de Medicina Interna da Universidade Federal de Pernambuco, Brazil
  1. * Corresponding author; email: norma.lucena{at}hotmail.com

Abstract

Tuberculosis clusters in families may be due to increased household exposure, shared genetic factors or both. Household contact studies are useful to control exposure, since socio-economical and environmental conditions are similar to all subjects, allowing the evaluation of the contribution of relatedness to disease development. In this study we evaluated the familial aggregation of tuberculosis using relatedness and a specific inherited marker (HLA-DRB1). Fifty families, which had at least two cases of tuberculosis diagnosed within the past five 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 health household contacts. Compared to unrelated contacts, the relative risk for tuberculosis adjusted for age was 1.38(95%CI:0.86-2.21). 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). This household contact model together with the utilization of two genetic variables permitted the evaluation of genetic factors contributing towards tuberculosis development.

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