TYMS Polymorphisms and Responsiveness to or Toxicity of Methotrexate in Rheumatoid Arthritis

Overview

Journal Z Rheumatol

Publisher Springer

Specialty Rheumatology

Date 2018 Jan 31

PMID 29380036

Citations 5

Authors

Sang-Cheol Bae

Young Ho Lee

Affiliations

Soon will be listed here.

Abstract

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.

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Genetic Polymorphisms of TYMS, MTHFR, ATIC, MTR, and MTRR Are Related to the Outcome of Methotrexate Therapy for Rheumatoid Arthritis in a Chinese Population.

Lv S, Fan H, Li J, Yang H, Huang J, Shu X Front Pharmacol. 2018; 9:1390.

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References

Lee Y, Rho Y, Choi S, Ji J, Song G . PADI4 polymorphisms and rheumatoid arthritis susceptibility: a meta-analysis. Rheumatol Int. 2007; 27(9):827-33. DOI: 10.1007/s00296-007-0320-y. View

Banerjee D, Mayer-Kuckuk P, Capiaux G, Budak-Alpdogan T, Gorlick R, Bertino J . Novel aspects of resistance to drugs targeted to dihydrofolate reductase and thymidylate synthase. Biochim Biophys Acta. 2002; 1587(2-3):164-73. DOI: 10.1016/s0925-4439(02)00079-0. View

Higgins J, Thompson S . Quantifying heterogeneity in a meta-analysis. Stat Med. 2002; 21(11):1539-58. DOI: 10.1002/sim.1186. View

Takatori R, Takahashi K, Tokunaga D, Hojo T, Fujioka M, Asano T . ABCB1 C3435T polymorphism influences methotrexate sensitivity in rheumatoid arthritis patients. Clin Exp Rheumatol. 2006; 24(5):546-54. View

Scott D, Wolfe F, Huizinga T . Rheumatoid arthritis. Lancet. 2010; 376(9746):1094-108. DOI: 10.1016/S0140-6736(10)60826-4. View

Aletaha D, Smolen J . The rheumatoid arthritis patient in the clinic: comparing more than 1,300 consecutive DMARD courses. Rheumatology (Oxford). 2002; 41(12):1367-74. DOI: 10.1093/rheumatology/41.12.1367. View

DerSimonian R, Laird N . Meta-analysis in clinical trials. Control Clin Trials. 1986; 7(3):177-88. DOI: 10.1016/0197-2456(86)90046-2. View

Ghodke Y, Chopra A, Joshi K, Patwardhan B . Are Thymidylate synthase and Methylene tetrahydrofolate reductase genes linked with methotrexate response (efficacy, toxicity) in Indian (Asian) rheumatoid arthritis patients?. Clin Rheumatol. 2008; 27(6):787-9. DOI: 10.1007/s10067-008-0852-x. View

Grabar P, Logar D, Lestan B, Dolzan V . Genetic determinants of methotrexate toxicity in rheumatoid arthritis patients: a study of polymorphisms affecting methotrexate transport and folate metabolism. Eur J Clin Pharmacol. 2008; 64(11):1057-68. DOI: 10.1007/s00228-008-0521-7. View

10.

Lee Y, Bae S, Choi S, Ji J, Song G . Associations between vitamin D receptor polymorphisms and susceptibility to rheumatoid arthritis and systemic lupus erythematosus: a meta-analysis. Mol Biol Rep. 2010; 38(6):3643-51. DOI: 10.1007/s11033-010-0477-4. View

11.

Swierkot J, Slezak R, Karpinski P, Pawlowska J, Noga L, Szechinski J . 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. 2015; 125(3):152-61. DOI: 10.20452/pamw.2707. View

12.

Felson D, Anderson J, Meenan R . The comparative efficacy and toxicity of second-line drugs in rheumatoid arthritis. Results of two metaanalyses. Arthritis Rheum. 1990; 33(10):1449-61. DOI: 10.1002/art.1780331001. View

13.

Borman P, Tasbas O, Karabulut H, Tukun A, Yorgancioglu R . Thymidylate synthase genetic polymorphism and plasma total homocysteine level in a group of Turkish patients with rheumatoid arthritis: relationship with disease activity and methotrexate toxicity. Rev Bras Reumatol. 2015; 55(6):485-92. DOI: 10.1016/j.rbr.2014.12.001. View

14.

Mandola M, Stoehlmacher J, Zhang W, Groshen S, Yu M, Iqbal S . A 6 bp polymorphism in the thymidylate synthase gene causes message instability and is associated with decreased intratumoral TS mRNA levels. Pharmacogenetics. 2004; 14(5):319-27. DOI: 10.1097/00008571-200405000-00007. View

15.

Lee Y, Woo J, Choi S, Ji J, Song G . Associations between osteoprotegerin polymorphisms and bone mineral density: a meta-analysis. Mol Biol Rep. 2009; 37(1):227-34. DOI: 10.1007/s11033-009-9637-9. View

16.

Egger M, Smith G, Phillips A . Meta-analysis: principles and procedures. BMJ. 1998; 315(7121):1533-7. PMC: 2127925. DOI: 10.1136/bmj.315.7121.1533. View

17.

Ulrich C, Bigler J, Velicer C, GREENE E, Farin F, Potter J . Searching expressed sequence tag databases: discovery and confirmation of a common polymorphism in the thymidylate synthase gene. Cancer Epidemiol Biomarkers Prev. 2001; 9(12):1381-5. View

18.

Lima A, Seabra V, Bernardes M, Azevedo R, Sousa H, Medeiros R . Role of key TYMS polymorphisms on methotrexate therapeutic outcome in portuguese rheumatoid arthritis patients. PLoS One. 2014; 9(10):e108165. PMC: 4184792. DOI: 10.1371/journal.pone.0108165. View

19.

Kumagai K, Hiyama K, Oyama T, Maeda H, Kohno N . Polymorphisms in the thymidylate synthase and methylenetetrahydrofolate reductase genes and sensitivity to the low-dose methotrexate therapy in patients with rheumatoid arthritis. Int J Mol Med. 2003; 11(5):593-600. View

20.

Kremer J . Toward a better understanding of methotrexate. Arthritis Rheum. 2004; 50(5):1370-82. DOI: 10.1002/art.20278. View