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<article xsi:noNamespaceSchemaLocation="http://jats.nlm.nih.gov/publishing/1.1/xsd/JATS-journalpublishing1-mathml3.xsd" dtd-version="1.1" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"><front><journal-meta><journal-id journal-id-type="publisher-id">DH</journal-id><journal-title-group><journal-title>Dermatological Health</journal-title></journal-title-group><issn>3083-4775</issn><eissn>2981-8206</eissn><publisher><publisher-name>Bio-Byword Scientific Publishing Pty. Ltd.</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="doi">10.26689/dh.v2i1.6496</article-id><article-categories><subj-group subj-group-type="heading"><subject>Article</subject></subj-group></article-categories><title>Influence of ABCB1 3435C&gt;T Polymorphism on Methotrexate Safety in Patients with Psoriasis — A Secondary Publication</title><url>https://artdesignp.com/journal/DH/2/1/10.26689/dh.v2i1.6496</url><author>КubanovАlexey А.,АsoskovaАnastasiia V.,ZastrozhinMichael S.,SozaevaZhannet A.,SychevDmitry A.</author><pub-date pub-type="publication-year"><year>2024</year></pub-date><volume>2</volume><issue>1</issue><history><date date-type="pub"><published-time>2024-03-29</published-time></date></history><abstract>Background: Methotrexate is a highly effective systemic treatment for moderate to severe psoriasis, but drug toxicity may limit its use. Recent evidence suggests that it is necessary to take into account the individual characteristics of methotrexate pharmacokinetics, which are determined by the presence of polymorphisms of genes encoding methotrexate carrier proteins, to predict the risk of methotrexate-induced toxicity. Aim: The research aims to assess the associations of ABCB1 rs1045642 (3435C&amp;gt;T) polymorphism with methotrexate safety for patients with moderate and severe psoriasis. Methods: The study included 75 psoriasis patients treated with methotrexate with 21 days of follow-up duration. Data on adverse drug reactions (ADR) were collected using a clinically structured questionnaire, and complete and biochemical blood tests, and urinalysis were performed. The severity of ADR was assessed using visual analog scales and the CTCAE toxicity scale. The severity of gastrointestinal ADR was assessed using the GSRS questionnaire. Genotyping was carried out by real-time PCR. Results: Gastrointestinal toxicity was detected in 38 patients (50.67%). The mean GSRS score was 7.97 ± 9.18. Analysis of differences in the ADR incidence showed the presence of statistically significant differences in the frequency of ADR in the gastrointestinal tract: the toxic effect of methotrexate was more often observed in carriers of the T allele of the ABCB1 rs1045642 polymorphism (3435C&amp;gt;T), (CC: 2 (14.3%), TC: 18 (52.9%), TT: 18 (66.7%), P = 0.006). Binomial regression demonstrated the presence of a statistically significant effect of the rs1045642 single-nucleotide polymorphism of the ABCB1 gene on the incidence of ADR from the gastrointestinal tract (OR = 8.64, P = 0.008). Conclusion: An association of ABCB1 rs1045642 single-nucleotide polymorphism with the safety of methotrexate therapy in patients with moderate and severe psoriasis was revealed. The data obtained can be used to personalize the prescription of methotrexate to psoriasis patients.</abstract><keywords/></article-meta></front><body/><back><ref-list><ref id="B1" content-type="article"><label>1</label><element-citation publication-type="journal"><p>Psoriasis. Clinical recommendations, 2020, Approved by the All-Russian Public Organization “Russian Society of Dermatovenerologists and Cosmetologists” January 15, 2020, Approved by the Scientific and Practical Council of the Ministry of Health of the Russian Federation.</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B2" content-type="article"><label>2</label><element-citation publication-type="journal"><p>Parisi R, Iskandar IYK, Kontopantelis E, 2020, National, Regional, and Worldwide Epidemiology of Psoriasis: Systematic Analysis and Modelling Study. BMJ, 2020(369): 1–15. http://doi.org/10.1136/bmj.m1590</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B3" content-type="article"><label>3</label><element-citation publication-type="journal"><p>Lebwohl M, 2005, Clinician’s Paradigm in the Treatment of Psoriasis. J Am Acad Dermatol, 53(1): S59–69. http://doi.org/10.1016/j.jaad.2005.04.031</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B4" content-type="article"><label>4</label><element-citation publication-type="journal"><p>Chikin VV, Znamenskaya LF, Minaeva AA, 2014, Pathogenic Aspects of Treatment of Psoriatic Patients. Vestnik Dermatologii Ivenerologii, 2014(5): 86–90.</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B5" content-type="article"><label>5</label><element-citation publication-type="journal"><p>West J, Ogston S, Foerster J, 2016, Safety and Efficacy of Methotrexate in Psoriasis: A Meta-Analysis of Published Trials. PLoS One, 11(5): e0153740. http://doi.org/10.1371/journal.pone.0153740</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B6" content-type="article"><label>6</label><element-citation publication-type="journal"><p>Yazici Y, Sokka T, Kautiainen H, et al., 2005, Long Term Safety of Methotrexate in Routine Clinical Care: Discontinuation is Unusual and Rarely the Result of Laboratory Abnormalities. Ann Rheum Dis, 64(2): 207–211. http://doi.org/10.1136/ard.2004.023408</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B7" content-type="article"><label>7</label><element-citation publication-type="journal"><p>Bedoui Y, Guillot X, Sélambarom J, et al., 2019, Methotrexate an Old Drug with New Tricks. Int J Mol Sci, 20(20): 5023. http://doi.org/10.3390/ijms20205023</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B8" content-type="article"><label>8</label><element-citation publication-type="journal"><p>Ray-Jones H, Eyre S, Barton A, et al., 2016, One SNP at a Time: Moving Beyond GWAS in Psoriasis. J Invest Dermatol, 136(3): 567–573. http://doi.org/10.1016/j.jid.2015.11.025</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B9" content-type="article"><label>9</label><element-citation publication-type="journal"><p>Sutherland A, Power RJ, Rahman P, et al., 2016, Pharmacogenetics and Pharmacogenomics in Psoriasis Treatment: Current Challenges and Future Prospects. Expert Opin Drug Metab Toxicol, 12(8): 923–935. http://doi.org/10.1080/17425255.2016.1194394</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B10" content-type="article"><label>10</label><element-citation publication-type="journal"><p>Sychjov DA, 2011, Recommendations for the Use of Pharmacogenetic Testing in Clinical. Kachestvennaya Klinicheskaya Praktika, 2011(1): 3–10.</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B11" content-type="article"><label>11</label><element-citation publication-type="journal"><p>Lima A, Bernardes M, Azevedo R, et al., 2014, SLC19A1, SLC46A1 and SLCO1B1 Polymorphisms as Predictors of Methotrexate-Related Toxicity in Portuguese Rheumatoid Arthritis Patients. Toxicological Sciences, 142(1): 196–209. http://doi.org/10.1093/toxsci/kfu162</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B12" content-type="article"><label>12</label><element-citation publication-type="journal"><p>Whetstine JR, Gifford AJ, Witt T, et al., 2001, Single Nucleotide Polymorphisms in the Human Reduced Folate Carrier: Characterization of a High-Frequency G/A Variant at Position 80 and Transport Properties of the His(27) and Arg(27) Carriers. Clin Cancer Res, 7(11): 3416–3422.</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B13" content-type="article"><label>13</label><element-citation publication-type="journal"><p>Marzolini C, Paus E, Buclin T, et al., 2004, Polymorphisms in Human MDR1 (P-Glycoprotein): recent Advances and Clinical Relevance. Clin Pharmacol Ther, 75(1): 13–33. http://doi.org/10.1016/j.clpt.2003.09.012</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B14" content-type="article"><label>14</label><element-citation publication-type="journal"><p>Hallas J, Harvald B, Gram LF, et al., 1990, Drug Related Hospital Admissions: The Role of Definitions and Intensity of Data Collection, and the Possibility of Prevention. J Intern Med, 228(2): 83–90. http://doi.org/10.1111/j.1365-2796.1990.tb00199.x</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B15" content-type="article"><label>15</label><element-citation publication-type="journal"><p>Stockwell DC, Slonim AD, 2006, Quality and Safety in the Intensive Care Unit. J Intensive Care Med, 21(4): 199–210. http://doi.org/10.1177/0885066606287079</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B16" content-type="article"><label>16</label><element-citation publication-type="journal"><p>Cvetov VM, 2007, Monitoring of Adverse Reactions of Drugs in an Outpatient Clinic at the Present Stage, dissertation, Chelyabinsk, 130.</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B17" content-type="article"><label>17</label><element-citation publication-type="journal"><p>US Department of Health and Human Services, National Institutes of Health, National Cancer Institute, 2017, Common Terminology Criteria for Adverse Events (CTCAE) Version 5, viewed January 6, 2022, https://ctep.cancer.gov/protocoldevelopment/electronic_applications/docs/CTCAE_v5_Quick_Reference_8.5x11.pdf</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B18" content-type="article"><label>18</label><element-citation publication-type="journal"><p>Svedlund J, Sjödin I, Dotevall G, 1988, GSRS-A Clinical Rating Scale for Gastrointestinal Symptoms in Patients with Irritable Bowel Syndrome and Peptic Ulcer Disease. Dig Dis Sci, 33(2): 129–134. http://doi.org/10.1007/BF01535722</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B19" content-type="article"><label>19</label><element-citation publication-type="journal"><p>Busto U, Naranjo CA, Sellers EM, 1982, Comparison of Two Recently Published Algorithms for Assessing the Probability of Adverse Drug Reactions. Br J Clin Pharmacol, 13(2): 223–227. http://doi.org/10.1111/j.1365-2125.1982.tb01361.x</p><pub-id pub-id-type="doi"/></element-citation></ref></ref-list></back></article>
