{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,22]],"date-time":"2026-01-22T05:20:46Z","timestamp":1769059246638,"version":"3.49.0"},"reference-count":32,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2020,4,18]],"date-time":"2020-04-18T00:00:00Z","timestamp":1587168000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J Biochem &amp; Molecular Tox"],"published-print":{"date-parts":[[2020,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Methotrexate (MTX), one of the important disease\u2010modifying anti\u2010rheumatic drugs, is the first\u2010line drug for rheumatoid arthritis (RA) treatment. However, its adverse drug effects (ADEs) often lead to the abortion of MTX therapy. Human organic anion\u2010transporting polypeptide 1A2 (OATP1A2, also referred as OATP\u2010A or OATP1) encoded by SLCO1A2 gene is an important isoform of the solute carrier transporter (SLC) family. It is known to participate in the cellular uptake of MTX. In our previous study, we identified four OATP1A2 natural variants (E184K, D185N, T259P, and D288N) with impaired MTX uptake activity. This study aimed to evaluate the association of the SLCO1A2 genetic variations encoding these OATP1A2 variants and MTX\u2010related toxicity in RA patients. A total of 60 RA patients were genotyped for these four polymorphisms (G550A, G553A, A775C, and G862A). The association between SLCO1A2 genetic variations and MTX toxicity was analyzed by binary logistic regression analysis. Single nucleotide polymorphisms (SNPs) analysis revealed that A775C and G862A SNPs were not detected in RA patients enrolled in this study, and the presence of 550AA genotype was associated with a high risk of MTX ADEs. Haplotype analysis revealed that H3 (H3\u2009=\u2009AG) showed a high risk of MTX ADEs. Furthermore, there was a significant association of 550AA genotype and impaired MTX disposition, which might be the cause of the increased incidence of MTX ADEs in RA patients. Therefore, genetic variations in SLCO1A2 gene are risk factors for MTX toxicity and its information contributes to the prediction of MTX\u2010related toxicity in RA treatment.<\/jats:p>","DOI":"10.1002\/jbt.22513","type":"journal-article","created":{"date-parts":[[2020,4,18]],"date-time":"2020-04-18T08:28:41Z","timestamp":1587198521000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Association between SLCO1A2 genetic variation and methotrexate toxicity in human rheumatoid arthritis treatment"],"prefix":"10.1002","volume":"34","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5339-4037","authenticated-orcid":false,"given":"Jiayi","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Rheumatology, Shanghai East Hospital Tongji University School of Medicine  Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jun","family":"Yin","sequence":"additional","affiliation":[{"name":"Department of Nephrology The Affiliated Wuxi No. 2 People's Hospital of Nanjing Medical University  Wuxi Jiangsu China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wei","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Rheumatology, Shanghai East Hospital Tongji University School of Medicine  Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chunyuan","family":"Xiao","sequence":"additional","affiliation":[{"name":"Department of Rheumatology, Shanghai East Hospital Tongji University School of Medicine  Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jie","family":"Han","sequence":"additional","affiliation":[{"name":"Department of Rheumatology, Shanghai East Hospital Tongji University School of Medicine  Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fanfan","family":"Zhou","sequence":"additional","affiliation":[{"name":"Sydney Pharmacy School The University of Sydney  Sydney New South Wales Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2020,4,18]]},"reference":[{"key":"e_1_2_5_2_1","doi-asserted-by":"publisher","DOI":"10.2147\/IJGM.S45929"},{"key":"e_1_2_5_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41413-018-0016-9"},{"key":"e_1_2_5_4_1","doi-asserted-by":"publisher","DOI":"10.1136\/rmdopen-2015-000057"},{"key":"e_1_2_5_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.hcl.2010.09.002"},{"key":"e_1_2_5_6_1","first-page":"473","volume":"58","author":"Swierkot J.","year":"2006","journal-title":"Pharmacol. 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