Login Register Cart 0
Generic placeholder image

Current Pharmaceutical Design

Editor-in-Chief

ISSN (Print): 1381-6128
ISSN (Online): 1873-4286

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe
Research Article

Associations Between microRNA-related Genetic Polymorphisms and Clinical Response to Methotrexate in Chinese Rheumatoid Arthritis Patients

Author(s): Qin-Wen Wen, Chong-Jing Chen, Han-Qing Zhang, Hang Yu, Zhen Zeng, Ting Jin, Ting-Hui Wang, Wen Qin, Hua Huang, Xiu-Di Wu* and Han Cen*

Volume 28, Issue 38, 2022

Published on: 28 October, 2022

Page: [3167 - 3173] Pages: 7

DOI: 10.2174/1381612829666221025154714

Price: $65

conference banner
Abstract

Background: Emerging evidence indicates that microRNA (miRNA)-related genetic polymorphisms are strongly involved in the post-transcriptional regulation of the expression of pharmacokinetics and pharmacodynamics- related genes, therefore contributing to the genetic variability of drug response.

Objective: To investigate the associations of miRNA-related genetic polymorphisms, including miRNA-5189 rs562929801, miRNA-595 rs4909237, SLCO1A2 rs4149009 and MTHFR rs3737966, and clinical response to methotrexate in Chinese rheumatoid arthritis patients.

Methods: One hundred patients treated with MTX for approximately 3 months were prospectively followed up to evaluate the clinical response according to European League Against Rheumatism (EULAR) good and moderate response, disease activity score in 28 joint counts - erythrocyte sedimentation rate (DAS28-ESR) low disease activity (LDA) and remission (REM), change in DAS28-ESR (ΔDAS28-ESR) and ΔDAS28-ESR > 0.6. Genetic polymorphisms were genotyped utilizing the HI-SNP technology.

Results: Of the 100 patients with a mean age of 52.23 ± 12.71 years, 81 patients were female (81.00%). After adjusting potential confounders, the major allele of miRNA-5189 rs562929801 was found to be significantly associated with EULAR response (A/A + A/G versus G/G, RR = 0.81, 95% CI = 0.67-0.99, P = 0.04) and ΔDAS28-ESR > 0.6 under dominant model (A/A + A/G versus G/G, RR = 0.83, 95% CI = 0.71-0.98, P = 0.03). However, nonsignificant evidence was detected for the remaining three miRNA-related genetic polymorphisms in neither univariable analysis nor multivariable analysis.

Conclusion: Our results indicated that miRNA-5189 rs562929801 was significantly associated with clinical response to MTX, and this association warrants further replication studies with larger sample sizes.

« Previous
[1]
Burmester, G.R.; Pope, J.E. Novel treatment strategies in rheumatoid arthritis. Lancet, 2017, 389(10086), 2338-2348.
[http://dx.doi.org/10.1016/S0140-6736(17)31491-5] [PMID: 28612748]
[2]
Fraenkel, L.; Bathon, J.M.; England, B.R. 2021 American college of rheumatology guideline for the treatment of rheumatoid arthritis. Arthritis Rheumatol., 2021, 73(7), 1108-1123.
[http://dx.doi.org/10.1002/art.41752] [PMID: 34101376]
[3]
Smolen, J.S.; Landewé, R.B.M.; Bijlsma, J.W.J. EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2019 update. Ann. Rheum. Dis., 2020, 79(6), 685-699.
[http://dx.doi.org/10.1136/annrheumdis-2019-216655] [PMID: 31969328]
[4]
Lau, C.S.; Chia, F.; Dans, L. 2018 update of the APLAR recommendations for treatment of rheumatoid arthritis. Int. J. Rheum. Dis., 2019, 22(3), 357-375.
[http://dx.doi.org/10.1111/1756-185X.13513] [PMID: 30809944]
[5]
Chatzidionysiou, K.; Sfikakis, P.P. Low rates of remission with methotrexate monotherapy in rheumatoid arthritis: Review of randomised controlled trials could point towards a paradigm shift. RMD Open, 2019, 5(2), e000993.
[http://dx.doi.org/10.1136/rmdopen-2019-000993] [PMID: 31413870]
[6]
Hazlewood, G.S.; Barnabe, C.; Tomlinson, G.; Marshall, D.; Devoe, D.; Bombardier, C. Methotrexate monotherapy and methotrexate combination therapy with traditional and biologic disease modifying antirheumatic drugs for rheumatoid arthritis: Abridged Cochrane systematic review and network meta-analysis. BMJ, 2016, 353, i1777.
[http://dx.doi.org/10.1136/bmj.i1777] [PMID: 27102806]
[7]
Finckh, A.; Liang, M.H.; van Herckenrode, C.M.; de Pablo, P. Long-term impact of early treatment on radiographic progression in rheumatoid arthritis: A meta-analysis. Arthritis Rheum., 2006, 55(6), 864-872.
[http://dx.doi.org/10.1002/art.22353] [PMID: 17139662]
[8]
Legrand, J.; Kirchgesner, T.; Sokolova, T.; Vande Berg, B.; Durez, P. Early clinical response and long-term radiographic progression in recent-onset rheumatoid arthritis: Clinical remission within six months remains the treatment target. Joint Bone Spine, 2019, 86(5), 594-599.
[http://dx.doi.org/10.1016/j.jbspin.2019.03.008] [PMID: 30928534]
[9]
ten Klooster, P.M.; Oude Voshaar, M.A.H.; Fakhouri, W.; de la Torre, I.; Nicolay, C.; van de Laar, M.A.F.J. Long-term clinical, functional, and cost outcomes for early rheumatoid arthritis patients who did or did not achieve early remission in a real-world treat-to-target strategy. Clin. Rheumatol., 2019, 38(10), 2727-2736.
[http://dx.doi.org/10.1007/s10067-019-04600-7] [PMID: 31161488]
[10]
Roden, D.M.; McLeod, H.L.; Relling, M.V. Pharmacogenomics. Lancet, 2019, 394(10197), 521-532.
[http://dx.doi.org/10.1016/S0140-6736(19)31276-0] [PMID: 31395440]
[11]
Jekic, B.; Maksimovic, N.; Damnjanovic, T. Methotrexate pharmacogenetics in the treatment of rheumatoid arthritis. Pharmacogenomics, 2019, 20(17), 1235-1245.
[http://dx.doi.org/10.2217/pgs-2019-0121] [PMID: 31648623]
[12]
Latini, A.; Borgiani, P.; Novelli, G.; Ciccacci, C. miRNAs in drug response variability: Potential utility as biomarkers for personalized medicine. Pharmacogenomics, 2019, 20(14), 1049-1059.
[http://dx.doi.org/10.2217/pgs-2019-0089] [PMID: 31559917]
[13]
Zanger, U.M.; Klein, K.; Kugler, N.; Petrikat, T.; Ryu, C.S. Epigenetics and MicroRNAs in pharmacogenetics. Adv. Pharmacol., 2018, 83, 33-64.
[http://dx.doi.org/10.1016/bs.apha.2018.02.003] [PMID: 29801581]
[14]
Detassis, S.; Grasso, M.; Del Vescovo, V.; Denti, M.A. microRNAs make the call in cancer personalized medicine. Front. Cell Dev. Biol., 2017, 5, 86.
[http://dx.doi.org/10.3389/fcell.2017.00086] [PMID: 29018797]
[15]
Bartel, D.P. MicroRNAs: Target recognition and regulatory functions. Cell, 2009, 136(2), 215-233.
[http://dx.doi.org/10.1016/j.cell.2009.01.002] [PMID: 19167326]
[16]
Iparraguirre, L.; Gutierrez-Camino, A.; Umerez, M. MiR-pharmacogenetics of methotrexate in childhood B-cell acute lymphoblastic leukemia. Pharmacogenet. Genomics, 2016, 26(11), 517-525.
[http://dx.doi.org/10.1097/FPC.0000000000000245] [PMID: 27649261]
[17]
Wang, S.; Zeng, W.; Wu, W.; Sun, L.; Yan, D. Association between a microRNA binding site polymorphism in SLCO1A2 and the risk of delayed methotrexate elimination in Chinese children with acute lymphoblastic leukemia. Leuk. Res., 2018, 65, 61-66.
[http://dx.doi.org/10.1016/j.leukres.2018.01.004] [PMID: 29306656]
[18]
Wang, S.M.; Zeng, W.X.; Wu, W.S.; Sun, L.L.; Yan, D. Association between MTHFR microRNA binding site polymorphisms and methotrexate concentrations in Chinese pediatric patients with acute lymphoblastic leukemia. J. Gene Med., 2017, 19(11), e2990.
[http://dx.doi.org/10.1002/jgm.2990] [PMID: 28990296]
[19]
Cen, H.; Wen, Q.W.; Zhang, H.Q. Associations between genetic polymorphisms within transporter genes and clinical response to methotrexate in Chinese rheumatoid arthritis patients: A pilot study. Pharm. Genomics Pers. Med., 2022, 15, 327-339.
[http://dx.doi.org/10.2147/PGPM.S350417] [PMID: 35437350]
[20]
Arnett, F.C.; Edworthy, S.M.; Bloch, D.A. The american rheumatism association 1987 revised criteria for the classification of rheumatoid arthritis. Arthritis Rheum., 1988, 31(3), 315-324.
[http://dx.doi.org/10.1002/art.1780310302] [PMID: 3358796]
[21]
Aletaha, D.; Neogi, T.; Silman, A.J. 2010 Rheumatoid arthritis classification criteria: An American college of rheumatology/european league against rheumatism collaborative initiative. Arthritis Rheum., 2010, 62(9), 2569-2581.
[http://dx.doi.org/10.1002/art.27584] [PMID: 20872595]
[22]
Prevoo, M.L.L. Van’T Hof MA, Kuper HH, Van Leeuwen MA, Van De Putte LBA, Van Riel PLCM. Modified disease activity scores that include twenty-eight-joint counts development and validation in a prospective longitudinal study of patients with rheumatoid arthritis. Arthritis Rheum., 1995, 38(1), 44-48.
[http://dx.doi.org/10.1002/art.1780380107] [PMID: 7818570]
[23]
van Gestel, A.M.; Prevoo, M.L.L.; van’t Hof, M.A.; van Rijswijk, M.H.; van de Putte, L.B.A.; van Riel, P.L.C.M. Development and validation of the european league against rheumatism response criteria for rheumatoid arthritis: Comparison with the preliminary American college of rheumatology and the world health organization/international league against rheumatism criteria. Arthritis Rheum., 1996, 39(1), 34-40.
[http://dx.doi.org/10.1002/art.1780390105] [PMID: 8546736]
[24]
Moszyńska A, Gebert M, Collawn JF, Bartoszewski R. SNPs in microRNA target sites and their potential role in human disease. Open Biol., 2017, 7(4), 170019.
[http://dx.doi.org/10.1098/rsob.170019] [PMID: 28381629]
[25]
Hernández-Preciado, M.R.; Morán-Moguel, M.C.; Dávalos-Rodríguez, I.P. miRNA-24 gene sequence, DHFR-829C-T genotypes, and methotrexate response in Mexican patients with rheumatoid arthritis. Genet. Test. Mol. Biomarkers, 2019, 23(3), 223-227.
[http://dx.doi.org/10.1089/gtmb.2018.0226] [PMID: 30758239]
[26]
Zhang, Y.; Tu, B.; Sha, Q.; Qian, J. Bone marrow mesenchymal stem cells-derived exosomes suppress miRNA-5189-3p to increase fibroblast-like synoviocyte apoptosis via the BATF2/JAK2/STAT3 signaling pathway. Bioengineered, 2022, 13(3), 6767-6780.
[http://dx.doi.org/10.1080/21655979.2022.2045844] [PMID: 35246006]
[27]
van de Steeg, E.; van Esch, A.; Wagenaar, E.; Kenworthy, K.E.; Schinkel, A.H. Influence of human OATP1B1, OATP1B3, and OATP1A2 on the pharmacokinetics of methotrexate and paclitaxel in humanized transgenic mice. Clin. Cancer Res., 2013, 19(4), 821-832.
[http://dx.doi.org/10.1158/1078-0432.CCR-12-2080] [PMID: 23243220]
[28]
Abud-Mendoza, C.; Martínez-Martínez, M.; Monsiváis-Urenda, A. González- Amaro R. Laboratory biomarkers for guiding therapy with methotrexate in rheumatoid arthritis. Curr. Pharm. Des., 2014, 21(2), 202-211.
[http://dx.doi.org/10.2174/1381612820666140825123632] [PMID: 25163739]
[29]
Wang, J.; Yin, J.; Li, W.; Xiao, C.; Han, J.; Zhou, F. Association between SLCO1A2 genetic variation and methotrexate toxicity in human rheumatoid arthritis treatment. J. Biochem. Mol. Toxicol., 2020, 34(8), e22513.
[http://dx.doi.org/10.1002/jbt.22513] [PMID: 32304147]
[30]
Cao, M.; Guo, M.; Wu, D.Q.; Meng, L. Pharmacogenomics of methotrexate: Current status and future outlook. Curr. Drug Metab., 2018, 19(14), 1182-1187.
[http://dx.doi.org/10.2174/1389200219666171227201047] [PMID: 29283070]

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy