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In a previous study, using a next generation sequencing approach, we found many rare variants and some functional polymorphisms in genes related to autoinflammatory syndromes (AID): <jats:italic>CECR1<\/jats:italic>, <jats:italic>MEFV<\/jats:italic>, <jats:italic>MVK<\/jats:italic>, <jats:italic>NLRP3<\/jats:italic>, <jats:italic>NOD2<\/jats:italic>, <jats:italic>PSTPIP1<\/jats:italic> and <jats:italic>TNFRSF1A<\/jats:italic> in our BD cohort. Our strategy did not allow us to establish either number of patients with variants, proportion of individuals accumulating them or relationship with other genetic factors. With the goal to answer these questions, the individual samples were sequenced. Additionally, three functional polymorphisms: <jats:italic>NLRP3<\/jats:italic> p.Gln703Lys, <jats:italic>NOD2<\/jats:italic> p.Arg702Trp and p.Val955Ile were genotyped using TaqMan assays. A total of 98 patients (27.6%) carried at least one rare variant and 13 of them (3.7%) accumulated two or three. Functional regression model analysis suggests epistatic interaction between B51 and <jats:italic>MEFV<\/jats:italic> (P\u2009=\u20090.003). A suggestive protective association of the minor allele of <jats:italic>NOD2<\/jats:italic> p.Arg702Trp (P\u2009=\u20090.01) was found in both, B51 positive and negative individuals. Therefore, a high percentage of patients with BD have rare variants in AID genes. Our results suggest that the association of MEFV with BD could be modulated by the HLA molecules; whereas the protective effect of NOD2 p.Arg702Trp would be independent of HLA.<\/jats:p>","DOI":"10.1038\/s41598-019-39113-5","type":"journal-article","created":{"date-parts":[[2019,2,26]],"date-time":"2019-02-26T11:49:58Z","timestamp":1551181798000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":25,"title":["Beh\u00e7et\u2019s disease and genetic interactions between HLA-B*51 and variants in genes of autoinflammatory syndromes"],"prefix":"10.1038","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6895-7875","authenticated-orcid":false,"given":"Sergio","family":"Burillo-Sanz","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marco-Antonio","family":"Montes-Cano","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jos\u00e9-Ra\u00fal","family":"Garc\u00eda-Lozano","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Israel","family":"Olivas-Mart\u00ednez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Norberto","family":"Ortego-Centeno","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francisco-Jos\u00e9","family":"Garc\u00eda-Hern\u00e1ndez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gerard","family":"Espinosa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Genaro","family":"Gra\u00f1a-Gil","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan","family":"S\u00e1nchez-Burs\u00f3n","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar\u00eda Rosa","family":"Juli\u00e1","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roser","family":"Solans","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ricardo","family":"Blanco","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana-Celia","family":"Barnosi-Mar\u00edn","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ricardo","family":"G\u00f3mez de la Torre","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patricia","family":"Fanlo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M\u00f3nica","family":"Rodr\u00edguez-Carballeira","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2869-7861","authenticated-orcid":false,"given":"Luis","family":"Rodr\u00edguez-Rodr\u00edguez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Teresa","family":"Camps","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Santos","family":"Casta\u00f1eda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan-Jose","family":"Alegre-Sancho","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Javier","family":"Mart\u00edn","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar\u00eda Francisca","family":"Gonz\u00e1lez-Escribano","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2019,2,26]]},"reference":[{"key":"39113_CR1","doi-asserted-by":"publisher","first-page":"901","DOI":"10.1111\/j.1365-2133.2007.08116.x","volume":"157","author":"E Alpsoy","year":"2007","unstructured":"Alpsoy, E. et al. 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