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MTX treatment is commonly associated with nausea. Large inter-individual variation exists in the level of MTX-induced nausea, possibly due to genetic factors.\n <\/jats:p>\n <\/jats:list-item>\n \n \n \n Purpose:<\/jats:italic>\n <\/jats:bold>\n To investigate whether MTX-induced nausea was associated with single nucleotide polymorphisms (SNPs) in genes encoding MTX-transporter proteins, a MTX metabolizing enzyme and a nausea receptor.\n <\/jats:p>\n <\/jats:list-item>\n <\/jats:list>\n <\/jats:p>\n <\/jats:sec>\n \n Findings<\/jats:title>\n \n \n \n \n \n Methods:<\/jats:italic>\n <\/jats:bold>\n Children aged \u22659\u2009years treated with MTX for JIA were eligible. MTX-induced nausea was registered by the children\u2019s completion of a nausea diary (min. 7\u2009days) and the parents\u2019 completion of the MTX intolerance severity score (MISS). The selected SNPs were:\n SLCO1B1<\/jats:italic>\n (rs4149056; rs4149081),\n SLCO1B3<\/jats:italic>\n (rs2117032),\n SLC19A1<\/jats:italic>\n (rs1051266),\n ABCC2<\/jats:italic>\n (rs2273697; rs3740066; rs717620),\n ABCB1<\/jats:italic>\n (rs2032582; rs1045642),\n MTHFR<\/jats:italic>\n (rs1801131, rs1801133),\n HTR3A<\/jats:italic>\n (rs1062613; rs1985242; rs1176713) and\n HTR3B<\/jats:italic>\n (rs1176744).\n <\/jats:p>\n <\/jats:list-item>\n \n \n \n Result:<\/jats:italic>\n <\/jats:bold>\n Enrolled were 121 JIA patients (82 girls: 39 boys) with a median age of 13.3\u2009years (IQR: 11.3\u201315.1). The median MTX dose was 9.7\u2009mg\/m\n 2<\/jats:sup>\n \/week (IQR: 9.0\u201310.9). The median MTX treatment duration prior to enrolment was 340\u2009days (IQR: 142\u2013766). The SNP analysis was available for 119 patients. MTX intolerance was associated with the genotype distribution of rs1801133 (\n MTHFR<\/jats:italic>\n ) (\n p<\/jats:italic>\n \u2009=\u20090.02). There was no additive effect of the minor alleles for any of the selected SNPs, nor any significant haplotype associations.\n <\/jats:p>\n <\/jats:list-item>\n <\/jats:list>\n <\/jats:p>\n <\/jats:sec>\n \n Conclusion<\/jats:title>\n \n \n \n \n \n Summary:<\/jats:italic>\n <\/jats:bold>\n MTX-induced nausea may be influenced by genetic polymorphisms in a MTX metabolizing enzyme (rs1801133; MTHFR).\n <\/jats:p>\n <\/jats:list-item>\n \n \n \n Implications:<\/jats:italic>\n <\/jats:bold>\n Further analyses involving inclusion of larger cohorts are needed to understand the impact of SNPs on MTX-induced nausea in JIA.\n <\/jats:p>\n <\/jats:list-item>\n <\/jats:list>\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1186\/s12969-021-00539-9","type":"journal-article","created":{"date-parts":[[2021,4,1]],"date-time":"2021-04-01T11:03:14Z","timestamp":1617274994000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Single nucleotide polymorphisms associated with methotrexate-induced nausea in juvenile idiopathic arthritis"],"prefix":"10.1186","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9490-1333","authenticated-orcid":false,"given":"Nini","family":"Kyvsgaard","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Torben Stamm","family":"Mikkelsen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thomas D.","family":"Als","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anne Estmann","family":"Christensen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thomas J.","family":"Corydon","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Troels","family":"Herlin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2021,4,1]]},"reference":[{"key":"539_CR1","doi-asserted-by":"publisher","unstructured":"Giannini EH, Brewer EJ, Kuzmina N, Shaikov A, Maximov A, Vorontsov I, et al. 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All participating families provided written informed consent prior to enrolment and the Central Denmark Region\u2019s research ethics committee approved the study (M-20110160). The study was observational and registered on\n \n (\n \n ).","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare that they have no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"51"}}