TYMS polymorphisms and responsiveness to or toxicity of methotrexate in rheumatoid arthritis; [TYMS-Polymorphismen und Empfindlichkeit gegenüber oder Toxizität von Methotrexat bei rheumatoider Arthritis]

被引：0
作者：
Bae S.-C. [1 ]
Lee Y.H. [2 ]
机构：
[1] Department of Rheumatology, Hospital for Rheumatic Diseases, Division of Rheumatology, Hanyang University, Hanyang
[2] Division of Rheumatology, Department of Internal Medicine, Korea University Anam Hospital, Korea University College of Medicine, 73, Inchon-ro, Seoul, 136-705, Seongbuk-gu
来源：
Zeitschrift für Rheumatologie | 2018年 / 77卷 / 9期
关键词：
Methotrexate; Rheumatoid arthritis; TYMS polymorphism;
D O I：
10.1007/s00393-018-0419-4
中图分类号：
学科分类号：
摘要：
Objective: The aim of this study was to investigate whether the thymidylate synthase (TYMS) 2R/3R and 6 bp I/D polymorphisms can predict the response to or toxicity of methotrexate (MTX) in patients with rheumatoid arthritis (RA). Methods: We conducted a meta-analysis of studies on the association between the TYMS 2R/3R and 6 bp I/D polymorphisms and non-responsiveness to or toxicity of MTX in RA patients. Results: A total of 11 studies involving 1613 patients were considered. Meta-analysis showed no association between the TYMS 2R/3R 3R allele and non-responsiveness to MTX therapy (odds ratio [OR] = 1.087, confidence interval [CI] = 0.682–1.731, p = 0.726). The meta-analysis indicated that there was no association between the TYMS 6 bp I/D D allele and non-responsiveness to MTX therapy (OR = 0.688, 95% CI = 0.281–1.683, p = 0.413). Meta-analysis revealed that the TYMS 2R/3R polymorphism was not associated with MTX toxicity, except for in a co-dominant model, and the TYMS 6 bp I/D polymorphism was not associated with MTX toxicity in all genetic models. Conclusions: This meta-analysis demonstrates that the TYMS 2R/3R and 6 bp I/D polymorphisms may not be associated with non-responsiveness to or toxicity of MTX therapy in RA patients. © 2018, Springer Medizin Verlag GmbH, ein Teil von Springer Nature.
引用
收藏
页码：824 / 832
页数：8
相关论文
共 33 条
  • [21] Lee Y.H., Woo J.H., Choi SJ et al Associations between osteoprotegerin polymorphisms and bone mineral density: a meta-analysis, Mol Biol Rep, 37, 1, pp. 227-234, (2009)
  • [22] Lima A., Seabra V., Bernardes M., Et al., Role of key TYMS polymorphisms on methotrexate therapeutic outcome in portuguese rheumatoid arthritis patients, PLoS ONE, 9, 10, (2014)
  • [23] Mandola M.V., Stoehlmacher J., Muller-Weeks S., Et al., A novel single nucleotide polymorphism within the 5’ tandem repeat polymorphism of the thymidylate synthase gene abolishes USF-1 binding and alters transcriptional activity, Cancer Res, 63, 11, pp. 2898-2904, (2003)
  • [24] Mandola M.V., Stoehlmacher J., Zhang W., Et al., A 6 bp polymorphism in the thymidylate synthase gene causes message instability and is associated with decreased intratumoral TS mRNA levels, Pharmacogenetics, 14, 5, pp. 319-327, (2004)
  • [25] Muralidharan N., Misra D.P., Jain V.K., Et al., Effect of thymidylate synthase (TYMS) gene polymorphisms with methotrexate treatment outcome in south Indian Tamil patients with rheumatoid arthritis, Clin Rheumatol, 36, pp. 1253-1259, (2017)
  • [26] Qiu Q., Huang J., Lin Y., Et al., Polymorphisms and pharmacogenomics for the toxicity of methotrexate monotherapy in patients with rheumatoid arthritis: A systematic review and meta-analysis, Medicine (Baltimore), 96, 11, (2017)
  • [27] Qiu Q., Huang J., Shu X., Et al., Polymorphisms and Pharmacogenomics for the Clinical Efficacy of Methotrexate in Patients with Rheumatoid Arthritis: A Systematic Review and Meta-analysis, Sci Rep, 7, (2017)
  • [28] Scott D.L., Wolfe F., Huizinga T.W., Rheumatoid arthritis, Lancet, 376, 9746, pp. 1094-1108, (2010)
  • [29] Swierkot J., Slezak R., Karpinski P., Et al., Associations between single-nucleotide polymorphisms of RFC-1, GGH, MTHFR, TYMS, and TCII genes and the efficacy and toxicity of methotrexate treatment in patients with rheumatoid arthritis, Pol Arch Med Wewn, 125, 3, pp. 152-161, (2015)
  • [30] Swierkot J., Szechinski J., Methotrexate in rheumatoid arthritis, Pharmacol Rep, 58, 4, pp. 473-492, (2006)
1234