{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,24]],"date-time":"2026-04-24T12:08:03Z","timestamp":1777032483666,"version":"3.51.4"},"reference-count":29,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2019,12,10]],"date-time":"2019-12-10T00:00:00Z","timestamp":1575936000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100006706","name":"Tampereen Tuberkuloosis\u00e4\u00e4ti\u00f6","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100006706","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Acta Paediatrica"],"published-print":{"date-parts":[[2020,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Aim<\/jats:title><jats:p>The aim of the study was to evaluate the association of <jats:italic>Toll\u2010like receptor 4<\/jats:italic> (<jats:italic>TLR4<\/jats:italic>) gene variations with osteitis risk after Bacillus Calmette\u2010Gu\u00e9rin (BCG) vaccination given at birth and with serum cytokine levels measured in adulthood.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We determined the <jats:italic>TLR4<\/jats:italic> rs4986790 single\u2010nucleotide polymorphism (SNP) in 132 study subjects with BCG osteitis in infancy and compared the genotype distributions and allele frequencies between them and population controls. Serum concentrations of 11 cytokines measured in adulthood were compared between study subjects with the wild vs variant <jats:italic>TLR4<\/jats:italic> rs4986790 genotype.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The genotypes and allele frequencies of the <jats:italic>TLR4<\/jats:italic> rs4986790 SNP did not differ between BCG osteitis cases and population controls. Instead, subjects with the variant genotype presented with lower serum interleukin (IL) concentrations of the pro\u2010inflammatory IL\u20106, IL\u201017A and IL\u201012 cytokines and with marginally lower interferon\u2010\u03b3 concentrations, but with higher serum anti\u2010inflammatory IL\u20104 concentration. The results concern also the <jats:italic>TLR4<\/jats:italic> rs4986791, since these two SNPs are co\u2010segregating in the Finnish population.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>The findings suggest that TLR4 has no significant role in the emergence of osteitis after newborn BCG vaccination, but the variant genotypes of the <jats:italic>TLR4<\/jats:italic> rs4986790 and rs4986791 may impair the production of pro\u2010inflammatory cytokines.<\/jats:p><\/jats:sec>","DOI":"10.1111\/apa.15104","type":"journal-article","created":{"date-parts":[[2019,11,22]],"date-time":"2019-11-22T11:43:45Z","timestamp":1574423025000},"page":"1417-1422","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["<i>Toll\u2010like receptor 4<\/i> polymorphisms were associated with low serum pro\u2010inflammatory cytokines in BCG osteitis survivors"],"prefix":"10.1111","volume":"109","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8153-1919","authenticated-orcid":false,"given":"Matti","family":"Korppi","sequence":"first","affiliation":[{"name":"Center for Child Health Research Faculty of Medicine and Life Sciences University of Tampere and University Hospital Tampere Finland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Johanna","family":"Ter\u00e4sj\u00e4rvi","sequence":"additional","affiliation":[{"name":"Institute of Biomedicine University of Turku Turku Finland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4654-7602","authenticated-orcid":false,"given":"Eero","family":"Lauhkonen","sequence":"additional","affiliation":[{"name":"Center for Child Health Research Faculty of Medicine and Life Sciences University of Tampere and University Hospital Tampere 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