{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T11:06:42Z","timestamp":1790680002789,"version":"4.1.0"},"reference-count":48,"publisher":"Oxford University Press (OUP)","license":[{"start":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T00:00:00Z","timestamp":1788912000000},"content-version":"am","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/501100002322","name":"Coordena\u00e7\u00e3o de Aperfei\u00e7oamento de Pessoal de N\u00edvel Superior","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100002322","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100016182","name":"Universidade Federal de Mato Grosso do Sul","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100016182","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003593","name":"Conselho Nacional de Desenvolvimento Cient\u00edfico e Tecnol\u00f3gico","doi-asserted-by":"publisher","award":["311016\/2025-1"],"award-info":[{"award-number":["311016\/2025-1"]}],"id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Paracoccidioidomycosis (PCM) is an endemic systemic mycosis in Latin America with marked clinical heterogeneity, suggesting a role for host immunogenetic factors. The NLRP3 inflammasome and IL-1\u03b2 signaling are important in antifungal immunity, but human genetic evidence remains limited. We evaluated whether single-nucleotide variants (SNVs) in inflammasome-related genes (NLRP1, NLRP3, CARD8, CASP1, and IL1B) are associated with PCM susceptibility, clinical form, and disease severity, including gene\u2013gene interactions.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We conducted a case\u2013control study including 346 individuals (154 people with PCM and 192 gp43-reactive healthy controls). Genetic associations were tested under multiple inheritance models using logistic regression adjusted for age, sex, smoking, and alcoholism. Epistatic interactions were assessed within the inflammasome\u2013IL-1\u03b2 axis, with Firth penalized logistic regression as a sensitivity analysis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>No single-SNV association with PCM susceptibility, clinical form, or severity remained significant after multiple-testing correction. Pairwise epistasis analysis identified an interaction between NLRP3 rs10754558 and IL1B rs1143634 associated with reduced PCM susceptibility (odds ratio [OR] = 0.34; 95% CI, .17\u2013.69; false discovery rate-adjusted P value [pFDR]= 0.015), supported by Firth regression. No significant epistatic interactions were found for clinical form or severity.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Genetic interactions within the inflammasome\u2013IL-1\u03b2 axis may contribute to PCM susceptibility. The interaction between NLRP3 rs10754558 and IL1B rs1143634 warrants validation in larger, independent cohorts.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/infdis\/jiag465","type":"journal-article","created":{"date-parts":[[2026,9,6]],"date-time":"2026-09-06T11:21:15Z","timestamp":1788693675000},"source":"Crossref","is-referenced-by-count":0,"title":["Epistatic Interactions Among Inflammasome Gene Variants Are Associated With Reduced Risk of Paracoccidioidomycosis"],"prefix":"10.1093","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8202-8151","authenticated-orcid":false,"given":"Sanderson da Silva","family":"Coelho","sequence":"first","affiliation":[{"name":"School of Medicine, Federal University of Mato Grosso do Sul , Campo Grande, Mato Grosso do Sul ,","place":["Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9184-3868","authenticated-orcid":false,"given":"B\u00e1rbara 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de","family":"Souza","sequence":"additional","affiliation":[{"name":"Lauro de Souza Lima Institute , Bauru, S\u00e3o Paulo ,","place":["Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9537-4889","authenticated-orcid":false,"given":"Grazielli Rocha","family":"de Rezende Romera","sequence":"additional","affiliation":[{"name":"State Health Department of Mato Grosso do Sul , Campo Grande, Mato Grosso do Sul ,","place":["Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dayane Alves de","family":"Melo","sequence":"additional","affiliation":[{"name":"Brazilian Air Force , Campo Grande, Mato Grosso do Sul ,","place":["Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Viviane Lima de","family":"Albuquerque","sequence":"additional","affiliation":[{"name":"Jaraguari City Hall , Jaraguari, Mato Grosso do Sul 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