{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T00:28:12Z","timestamp":1788827292515,"version":"build-2803163510"},"reference-count":26,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2025,12,25]],"date-time":"2025-12-25T00:00:00Z","timestamp":1766620800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100012190","name":"Ministry of Science and Higher Education of the Russian Federation","doi-asserted-by":"crossref","award":["075-15-2025-463"],"award-info":[{"award-number":["075-15-2025-463"]}],"id":[{"id":"10.13039\/501100012190","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JPM"],"abstract":"<jats:p>Background: Pharmacogenetic markers associated with the need to switch patients from methotrexate (MTX) to biologic agents in moderate-to-severe psoriasis remain insufficiently studied. The pharmacokinetics of MTX depend on the individual characteristics of the patient, as well as on the function of specific transporters and enzymes involved in its absorption, distribution, metabolism, and elimination; therefore, polymorphisms in genes encoding these proteins may be considered pharmacogenetic predictors of MTX intolerance or insufficient efficacy. This study aimed to investigate genetic variants associated with MTX intolerance or insufficient efficacy leading to therapy switch. Methods: A total of 80 patients with moderate-to-severe psoriasis were included: 43 who required switching from MTX to biologics and 37 who continued MTX therapy. Twelve polymorphisms in transporter and metabolism-related genes (ABCB1 (rs1045642), MTHFR (rs1801133), ABCB1 (rs1128503), ABCC2 (rs3740066), ABCC2 (rs717620), ABCG2 (rs2231137), GSTP1 (rs1695), SLC19A1 (rs1051266), COL18A1 (rs9977268), SLCO1B1 (rs2306283), SLCO1B1 (rs4149056), and ABCB1 (rs2229109)) were analyzed using next-generation sequencing. Results: Significant differences in genotype frequencies were observed for SLC19A1 rs1051266 (p = 0.03) and COL18A1 rs9977268 (p = 0.02). Carriers of the T allele in both genes were more frequent among patients requiring biologic therapy, suggesting a possible association with MTX intolerance or reduced efficacy. Conclusions: The study revealed an association between polymorphisms in the SLC19A1 rs1051266 and COL18A1 rs9977268 genes and the need to switch from MTX to biologic therapy in patients with moderate-to-severe psoriasis. These findings suggest that carriers of the C allele in these genes may have an increased risk of methotrexate intolerance.<\/jats:p>","DOI":"10.3390\/jpm16010005","type":"journal-article","created":{"date-parts":[[2025,12,26]],"date-time":"2025-12-26T02:07:58Z","timestamp":1766714878000},"page":"5","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Genetic Markers of Methotrexate Treatment Failure in Psoriasis"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-7977-5441","authenticated-orcid":false,"given":"Maria N.","family":"Vikhreva","sequence":"first","affiliation":[{"name":"Penza Institute for Advanced Medical Education\u2014Branch of the Federal State Budgetary Educational Institution of Further Professional Education \u201cRussian Medical Academy of Continuous Professional Education\u201d of the Ministry of Healthcare of the Russian Federation, 8A Stasov Str., Penza 440060, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4479-3095","authenticated-orcid":false,"given":"Lavrenty G.","family":"Danilov","sequence":"additional","affiliation":[{"name":"Federal State Budgetary Educational Institution of Higher Education \u201cSt. Petersburg State University\u201d, 7-9 Universitetskaya Nab., Saint Petersburg 199034, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrey A.","family":"Martynov","sequence":"additional","affiliation":[{"name":"Federal State Budgetary Research Institution \u201cRussian Research Center of Surgery Named After Academician B.V. Petrovsky\u201d, Abrikosovsky Lane, 2, Moscow 119991, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8440-6598","authenticated-orcid":false,"given":"Olga A.","family":"Levashova","sequence":"additional","affiliation":[{"name":"Penza Institute for Advanced Medical Education\u2014Branch of the Federal State Budgetary Educational Institution of Further Professional Education \u201cRussian Medical Academy of Continuous Professional Education\u201d of the Ministry of Healthcare of the Russian Federation, 8A Stasov Str., Penza 440060, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-2744-2752","authenticated-orcid":false,"given":"Svetlana N.","family":"Tuchkova","sequence":"additional","affiliation":[{"name":"Federal State Budgetary Research Institution \u201cRussian Research Center of Surgery Named After Academician B.V. Petrovsky\u201d, Abrikosovsky Lane, 2, Moscow 119991, Russia"},{"name":"Federal State Budgetary Educational Institution of Further Professional Education \u201cRussian Medical Academy of Continuous Professional Education\u201d of the Ministry of Healthcare of the Russian Federation, Barrikadnaya Str. 2\/1, bld. 1, Moscow 125993, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9001-1499","authenticated-orcid":false,"given":"Sherzod P.","family":"Abdullaev","sequence":"additional","affiliation":[{"name":"Federal State Budgetary Research Institution \u201cRussian Research Center of Surgery Named After Academician B.V. Petrovsky\u201d, Abrikosovsky Lane, 2, Moscow 119991, Russia"},{"name":"Federal State Budgetary Educational Institution of Further Professional Education \u201cRussian Medical Academy of Continuous Professional Education\u201d of the Ministry of Healthcare of the Russian Federation, Barrikadnaya Str. 2\/1, bld. 1, Moscow 125993, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9307-4994","authenticated-orcid":false,"given":"Karin B.","family":"Mirzaev","sequence":"additional","affiliation":[{"name":"Federal State Budgetary Research Institution \u201cRussian Research Center of Surgery Named After Academician B.V. Petrovsky\u201d, Abrikosovsky Lane, 2, Moscow 119991, Russia"},{"name":"Federal State Budgetary Educational Institution of Further Professional Education \u201cRussian Medical Academy of Continuous Professional Education\u201d of the Ministry of Healthcare of the Russian Federation, Barrikadnaya Str. 2\/1, bld. 1, Moscow 125993, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7465-4504","authenticated-orcid":false,"given":"Andrey S.","family":"Glotov","sequence":"additional","affiliation":[{"name":"Federal Scientific and Clinical Center for Infectious Diseases of the Federal Medical Biological Agency of Russian Federation, 9A Professora Popova Str., Saint Petersburg 197022, Russia"},{"name":"Federal State Budgetary Scientific Institution \u201cThe D.O. Ott Research Institute of Obstetrics, Gynecology and Reproductology\u201d, 3 Mendeleevskaya Line, Saint Petersburg 199034, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0091-2224","authenticated-orcid":false,"given":"Oleg S.","family":"Glotov","sequence":"additional","affiliation":[{"name":"Federal Scientific and Clinical Center for Infectious Diseases of the Federal Medical Biological Agency of Russian Federation, 9A Professora Popova Str., Saint Petersburg 197022, Russia"},{"name":"Federal State Budgetary Scientific Institution \u201cThe D.O. Ott Research Institute of Obstetrics, Gynecology and Reproductology\u201d, 3 Mendeleevskaya Line, Saint Petersburg 199034, Russia"},{"name":"State Budgetary Healthcare Institution \u201cMoscow Scientific and Practical Center for Laboratory Research of the Moscow Healthcare Department\u201d, 49 Orekhovy Boulevard, bld. 1, Moscow 115580, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4496-3680","authenticated-orcid":false,"given":"Dmitry A.","family":"Sychev","sequence":"additional","affiliation":[{"name":"Federal State Budgetary Research Institution \u201cRussian Research Center of Surgery Named After Academician B.V. Petrovsky\u201d, Abrikosovsky Lane, 2, Moscow 119991, Russia"},{"name":"Federal State Budgetary Educational Institution of Further Professional Education \u201cRussian Medical Academy of Continuous Professional Education\u201d of the Ministry of Healthcare of the Russian Federation, Barrikadnaya Str. 2\/1, bld. 1, Moscow 125993, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,12,25]]},"reference":[{"key":"ref_1","unstructured":"Ministry of Healthcare of the Russian Federation (2025, August 20). Psoriasis. Clinical Guidelines, Available online: https:\/\/cr.minzdrav.gov.ru\/preview-cr\/234_2."},{"key":"ref_2","first-page":"1","article-title":"Update Aetiopathogenesis and Treatment of Psoriasis: A Literature Review","volume":"4","author":"Chen","year":"2023","journal-title":"J. Dermatol. Res."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"4699","DOI":"10.1007\/s11033-020-05481-9","article-title":"Molecular mechanism of action and pharmacokinetic properties of methotrexate","volume":"47","author":"Maksimovic","year":"2020","journal-title":"Mol. Biol. Rep."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1186\/s13075-015-0814-z","article-title":"Methotrexate polyglutamates as a potential marker of adherence to long-term therapy in children with juvenile idiopathic arthritis and juvenile dermatomyositis: An observational, cross-sectional study","volume":"17","author":"Hawwa","year":"2015","journal-title":"Arthritis Res. Ther."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1025","DOI":"10.1080\/17512433.2024.2416674","article-title":"Methotrexate polyglutamates","volume":"17","author":"Yang","year":"2024","journal-title":"Expert Rev. Clin. Pharmacol."},{"key":"ref_6","first-page":"254","article-title":"Methotrexate safety in psoriasis: An overview","volume":"76","author":"Asoskova","year":"2021","journal-title":"Ann. Russ. Acad. Med. Sci."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"231","DOI":"10.2147\/PTT.S328460","article-title":"Towards Personalized Medicine in Psoriasis: Current Progress","volume":"12","author":"Camela","year":"2022","journal-title":"Psoriasis"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1097\/CAD.0000000000001125","article-title":"Association between SLCO1B1 Polymorphism and Methotrexate-Induced Hepatotoxicity: A Systematic Review and Meta-Analysis","volume":"33","author":"Han","year":"2022","journal-title":"Anticancer Drugs"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"439","DOI":"10.1016\/j.det.2024.02.005","article-title":"The Role of Genetics on Psoriasis Susceptibility, Comorbidities, and Treatment Response","volume":"42","author":"Bui","year":"2024","journal-title":"Dermatol. Clin."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"7","DOI":"10.14412\/1996-7012-2020-3-7-18","article-title":"Early prescription of biological agents for immune-mediated inflammatory diseases: Opportunities and prospects. An expert\u2019s opinion","volume":"14","author":"Abdulganieva","year":"2020","journal-title":"Sovrem. Revmatol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"e14660","DOI":"10.1111\/dth.14660","article-title":"New generation biologics for the treatment of psoriasis and psoriatic arthritis: State of the art and considerations about the risk of infection","volume":"34","author":"Ceccarelli","year":"2021","journal-title":"Dermatol. Ther."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"369","DOI":"10.1080\/17425255.2021.1876661","article-title":"ABCB1, ABCG2, ABCC1, ABCC2, and ABCC3 drug transporter polymorphisms and their impact on drug bioavailability: What is our current understanding?","volume":"17","author":"Bruckmueller","year":"2021","journal-title":"Expert Opin. Drug Metab. Toxicol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1038\/s41573-023-00877-1","article-title":"Membrane transporters in drug development and as determinants of precision medicine","volume":"23","author":"Galetin","year":"2024","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Zhang, Q., Lin, J., Zhang, Z., Han, L., Huang, Q., Zhu, J., Wang, B., Fang, X., Zheng, Z., and Yawalkar, N. (2022). MTHFR polymorphism and folic acid supplementation influence serum homocysteine levels in psoriatic patients treated with methotrexate. J. Clin. Med., 11.","DOI":"10.3390\/jcm11154580"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"107459","DOI":"10.1016\/j.vph.2024.107459","article-title":"Endostatin in disease modulation: From cancer to beyond","volume":"158","author":"Anakha","year":"2025","journal-title":"Vascul. Pharmacol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"515","DOI":"10.1016\/j.ad.2016.12.001","article-title":"Angiogenesis in dermatology: Insights of molecular mechanisms and latest developments","volume":"108","author":"Richarz","year":"2017","journal-title":"Actas Dermosifiliogr."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"485","DOI":"10.1161\/ATVBAHA.107.159772","article-title":"Critical role of lipid raft redox signaling platforms in endostatin-induced coronary endothelial dysfunction","volume":"28","author":"Jin","year":"2008","journal-title":"Arter. Thromb. Vasc. Biol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"154","DOI":"10.1159\/000028396","article-title":"Glutathione S-transferase polymorphisms and their biological consequences","volume":"61","author":"Hayes","year":"2000","journal-title":"Pharmacology"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1007\/s00228-013-1623-4","article-title":"Pharmacogenetics of methotrexate in acute lymphoblastic leukaemia: Why still at the bench level?","volume":"70","author":"Kodidela","year":"2014","journal-title":"Eur. J. Clin. Pharmacol."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Taylor, Z.L., Vang, J., Lopez-Lopez, E., Oosterom, N., Mikkelsen, T., and Ramsey, L.B. (2021). Systematic review of pharmacogenetic factors that influence high-dose methotrexate pharmacokinetics in pediatric malignancies. Cancers, 13.","DOI":"10.3390\/cancers13112837"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"393","DOI":"10.1007\/s00280-022-04405-7","article-title":"Evaluation of cytogenetic and molecular markers with MTX-mediated toxicity in pediatric acute lymphoblastic leukemia patients","volume":"89","author":"Ramalingam","year":"2022","journal-title":"Cancer Chemother. Pharmacol."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Cwiklinska, M., Czogala, M., Kwiecinska, K., Madetko-Talowska, A., Szafarz, M., Pawinska, K., Wieczorek, A., Klekawka, T., Rej, M., and Stepien, K. (2020). Polymorphisms of SLC19A1 80 G>A, MTHFR 677 C>T, and tandem TS repeats influence pharmacokinetics, acute liver toxicity, and vomiting in children with acute lymphoblastic leukemia treated with high doses of methotrexate. Front. Pediatr., 8.","DOI":"10.3389\/fped.2020.00307"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1016\/j.addr.2017.07.014","article-title":"The good and the bad collagens of fibrosis: Their role in signaling and organ function","volume":"121","author":"Karsdal","year":"2017","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"e14727","DOI":"10.1111\/dth.14727","article-title":"Assessment of selected angiogenesis markers in the serum of middle-aged male patients with plaque psoriasis","volume":"34","author":"Socha","year":"2021","journal-title":"Dermatol. Ther."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1038\/tpj.2012.7","article-title":"Genetic polymorphisms in key methotrexate pathway genes are associated with response to treatment in rheumatoid arthritis patients","volume":"13","author":"Owen","year":"2013","journal-title":"Pharmacogenomics J."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1860","DOI":"10.1038\/sj.jid.5700808","article-title":"Polymorphisms in folate, pyrimidine, and purine metabolism are associated with efficacy and toxicity of methotrexate in psoriasis","volume":"127","author":"Campalani","year":"2007","journal-title":"J. Investig. Dermatol."}],"container-title":["Journal of Personalized Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2075-4426\/16\/1\/5\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,12,27]],"date-time":"2025-12-27T05:15:47Z","timestamp":1766812547000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2075-4426\/16\/1\/5"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,12,25]]},"references-count":26,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,1]]}},"alternative-id":["jpm16010005"],"URL":"https:\/\/doi.org\/10.3390\/jpm16010005","relation":{},"ISSN":["2075-4426"],"issn-type":[{"value":"2075-4426","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,12,25]]}}}