{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,31]],"date-time":"2026-10-31T06:15:36Z","timestamp":1793427336148,"version":"4.5.0"},"reference-count":36,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2018,11,27]],"date-time":"2018-11-27T00:00:00Z","timestamp":1543276800000},"content-version":"vor","delay-in-days":3,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"name":"Conselho Nacional de Desenvolvimento Cient\u00edfico e Tecnol\u00f3gico (CNPq) \/ Instituto"},{"name":"Nacional de Ci\u00eancia e Tecnologia","award":["573548\/2008-0"],"award-info":[{"award-number":["573548\/2008-0"]}]},{"name":"Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa do Rio de Janeiro","award":["E-26\/110.974\/2011"],"award-info":[{"award-number":["E-26\/110.974\/2011"]}]},{"DOI":"10.13039\/501100006507","name":"FIOCRUZ","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100006507","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["U01AI115940"],"award-info":[{"award-number":["U01AI115940"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2019,8,30]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>The role of genetic polymorphisms in latent tuberculosis (TB) infection and progression to active TB is not fully understood.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We tested the single-nucleotide polymorphisms (SNPs) rs5743708 (TLR2), rs4986791 (TLR4), rs361525 (TNFA), rs2430561 (IFNG) rs1143627 (IL1B) as risk factors for tuberculin skin test (TST) conversion or development of active TB in contacts of active TB cases. Contacts of microbiologically confirmed pulmonary TB cases were initially screened for longitudinal evaluation up to 24 months, with clinical examination and serial TST, between 1998 and 2004 at a referral center in Brazil. Data and biospecimens were collected from 526 individuals who were contacts of 177 active TB index cases. TST conversion was defined as induration \u22655 mm after a negative TST result (0 mm) at baseline or month 4 visit. Independent associations were tested using logistic regression models.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Among the 526 contacts, 60 had TST conversion and 44 developed active TB during follow-up. Multivariable regression analysis demonstrated that male sex (odds ratio [OR]: 2.3, 95% confidence interval [CI]: 1.1\u20134.6), as well as SNPs in TLR4 genes (OR: 62.8, 95% CI: 7.5\u2013525.3) and TNFA (OR: 4.2, 95% CI: 1.9\u20139.5) were independently associated with TST conversion. Moreover, a positive TST at baseline (OR: 4.7, 95% CI: 2.3\u20139.7) and SNPs in TLR4 (OR: 6.5, 95% CI: 1.1\u201336.7) and TNFA (OR: 12.4, 95% CI:5.1\u201330.1) were independently associated with incident TB.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>SNPs in TLR4 and TNFA predicted both TST conversion and active TB among contacts of TB cases in Brazil.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/cid\/ciy1001","type":"journal-article","created":{"date-parts":[[2018,11,20]],"date-time":"2018-11-20T15:11:58Z","timestamp":1542726718000},"page":"1027-1035","source":"Crossref","is-referenced-by-count":30,"title":["Polymorphisms in TLR4 and TNFA and Risk of Mycobacterium tuberculosis Infection and Development of Active Disease in Contacts of Tuberculosis Cases in Brazil: A Prospective Cohort Study"],"prefix":"10.1093","volume":"69","author":[{"given":"Juan Manuel","family":"Cubillos-Angulo","sequence":"first","affiliation":[{"name":"Instituto Gon\u00e7alo Moniz, Funda\u00e7\u00e3o Oswaldo Cruz, Salvador, Bahia"},{"name":"Faculdade de Medicina, Universidade Federal da Bahia, Salvador, Bahia"},{"name":"Multinational Organization Network Sponsoring Translational and Epidemiological Research (MONSTER) Initiative, Funda\u00e7\u00e3o Jos\u00e9 Silveira, Salvador, Bahia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar\u00eda B","family":"Arriaga","sequence":"additional","affiliation":[{"name":"Instituto Gon\u00e7alo Moniz, Funda\u00e7\u00e3o Oswaldo Cruz, Salvador, Bahia"},{"name":"Faculdade de Medicina, Universidade Federal da Bahia, Salvador, Bahia"},{"name":"Multinational Organization Network Sponsoring Translational and Epidemiological Research (MONSTER) Initiative, Funda\u00e7\u00e3o Jos\u00e9 Silveira, Salvador, Bahia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elis\u00e2ngela C","family":"Silva","sequence":"additional","affiliation":[{"name":"Programa Acad\u00eamico de Tuberculose, Faculdade de Medicina e Complexo Hospitalar HUCFF-IDT, Universidade Federal do Rio de Janeiro"},{"name":"Recognize the Biology Laboratory, Center of Bioscience and Biotechnology, State University of North Fluminense Darcy Ribeiro"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beatriz L A","family":"M\u00fcller","sequence":"additional","affiliation":[{"name":"Programa Acad\u00eamico de Tuberculose, Faculdade de Medicina e Complexo Hospitalar HUCFF-IDT, Universidade Federal do Rio de Janeiro"},{"name":"Laborat\u00f3rio de Gen\u00f4mica Funcional e Bioinform\u00e1tica, Instituto Oswaldo Cruz, Fiocruz, Rio de Janeiro"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniela M P","family":"Ramalho","sequence":"additional","affiliation":[{"name":"Programa Acad\u00eamico de Tuberculose, Faculdade de Medicina e Complexo Hospitalar HUCFF-IDT, Universidade Federal do Rio de Janeiro"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kiyoshi F","family":"Fukutani","sequence":"additional","affiliation":[{"name":"Instituto Gon\u00e7alo Moniz, Funda\u00e7\u00e3o Oswaldo Cruz, Salvador, Bahia"},{"name":"Multinational Organization Network Sponsoring Translational and Epidemiological Research (MONSTER) Initiative, Funda\u00e7\u00e3o Jos\u00e9 Silveira, Salvador, Bahia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pryscila F C","family":"Miranda","sequence":"additional","affiliation":[{"name":"Programa Acad\u00eamico de Tuberculose, Faculdade de Medicina e Complexo Hospitalar HUCFF-IDT, Universidade Federal do Rio de Janeiro"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adriana S R","family":"Moreira","sequence":"additional","affiliation":[{"name":"Programa Acad\u00eamico de Tuberculose, Faculdade de Medicina e Complexo Hospitalar HUCFF-IDT, Universidade Federal do Rio de Janeiro"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonio","family":"Ruffino-Netto","sequence":"additional","affiliation":[{"name":"Faculdade de Medicina de Ribeir\u00e3o Preto, Universidade de S\u00e3o Paulo, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jose R","family":"Lapa e Silva","sequence":"additional","affiliation":[{"name":"Programa Acad\u00eamico de Tuberculose, Faculdade de Medicina e Complexo Hospitalar HUCFF-IDT, Universidade Federal do Rio de Janeiro"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timothy R","family":"Sterling","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases, Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Afr\u00e2nio L","family":"Kritski","sequence":"additional","affiliation":[{"name":"Programa Acad\u00eamico de Tuberculose, Faculdade de Medicina e Complexo Hospitalar HUCFF-IDT, Universidade Federal do Rio de Janeiro"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martha M","family":"Oliveira","sequence":"additional","affiliation":[{"name":"Centro de Desenvolvimento Tecnol\u00f3gico em Sa\u00fade, Fundac\u0327a\u0303o Oswaldo Cruz, Rio de Janeiro, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6833-3811","authenticated-orcid":false,"given":"Bruno B","family":"Andrade","sequence":"additional","affiliation":[{"name":"Instituto Gon\u00e7alo Moniz, Funda\u00e7\u00e3o Oswaldo Cruz, Salvador, Bahia"},{"name":"Multinational Organization Network Sponsoring Translational and Epidemiological Research (MONSTER) Initiative, Funda\u00e7\u00e3o Jos\u00e9 Silveira, Salvador, Bahia"},{"name":"Division of Infectious Diseases, Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee"},{"name":"Wellcome Centre for Infectious Disease Research in 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