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We investigate the role of IGF-1\/IGF1R signaling in the context of gouty inflammation. Also, we test the gout and urate-associated <jats:italic>IGF1R<\/jats:italic> rs6598541 polymorphism for association with the inflammatory capacity of mononuclear cells. For this,\u00a0freshly isolated human peripheral blood mononuclear cells (PBMCs) were exposed to recombinant IGF-1 or anti-IGF1R neutralizing antibody in the presence or absence of solubilized urate, stimulated with LPS\/MSU crystals. Also, the\u00a0association of rs6598541 with <jats:italic>IGF1R<\/jats:italic> and protein expression and with ex vivo cytokine production levels after stimulation with gout specific stimuli was tested. Urate exposure was not associated with <jats:italic>IGF1R<\/jats:italic> expression in vitro or in vivo. Modulation of IGF1R did not alter urate-induced inflammation. Developing urate-induced trained immunity in vitro was not influenced in cells challenged with IGF-1 recombinant protein. Moreover,\u00a0the <jats:italic>IGF1R<\/jats:italic> rs6598541 SNP was not associated with cytokine production. Our results indicate that urate-induced inflammatory priming is not regulated by IGF-1\/IGF1R signaling in vitro. <jats:italic>IGF1R<\/jats:italic> rs6598541 status was not asociated with <jats:italic>IGF1R<\/jats:italic> expression or cytokine production in primary human PBMCs. This\u00a0study suggests that the role of IGF1R in gout is tissue-specific and may be more relevant in the control of urate levels rather than in inflammatory signaling in gout.<\/jats:p>","DOI":"10.1038\/s41598-024-53209-7","type":"journal-article","created":{"date-parts":[[2024,2,12]],"date-time":"2024-02-12T19:03:29Z","timestamp":1707764609000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["GWAS-identified hyperuricemia-associated IGF1R variant rs6598541 has a limited role in urate mediated inflammation in human mononuclear cells"],"prefix":"10.1038","volume":"14","author":[{"given":"Orsolya I.","family":"Gaal","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruiqi","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Drago\u0219","family":"Marginean","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Medeea","family":"Badii","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Georgiana","family":"Cab\u0103u","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ioana","family":"Hotea","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valentin","family":"Nica","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Doina","family":"Colcear","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"HINT Consortium","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leo A. 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