{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,16]],"date-time":"2025-10-16T07:04:15Z","timestamp":1760598255721,"version":"3.41.0"},"reference-count":31,"publisher":"Scientific Scholar","issue":"2","content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2023,8]]},"abstract":"<jats:sec>\n            <jats:title>Background &amp; objectives:<\/jats:title>\n            <jats:p>Imatinib mesylate (IM) is a reliable first line treatment for chronic myeloid leukaemia (CML). Nevertheless, despite promising results, a considerable proportion of patients develop resistance to the drug. Cytochrome P450 (CYP) enzymes play a crucial role in IM metabolism. Thus, point mutations in <jats:italic toggle=\"yes\">CYP<\/jats:italic> genes may modify IM enzyme activity resulting in insufficient treatment response. This investigation was aimed to identify the functional impact of <jats:italic toggle=\"yes\">CYP3A5*3<\/jats:italic>, <jats:italic toggle=\"yes\">CYP3A4*18<\/jats:italic> and <jats:italic toggle=\"yes\">CYP2B6*6<\/jats:italic> polymorphisms on the IM response in patients with CML in Azerbaijan.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods:<\/jats:title>\n            <jats:p>Genotyping of <jats:italic toggle=\"yes\">CYP3A5*3<\/jats:italic>, <jats:italic toggle=\"yes\">CYP3A4*18<\/jats:italic> and <jats:italic toggle=\"yes\">CYP2B6*6<\/jats:italic> was performed in 153 patients (102 IM non-responders and 51 IM responders) with CML by the PCR-restriction fragment length polymorphism (RFLP) assays. The odds ratios (ORs) with 95 per cent confidence intervals (CIs) were applied to assess the association between allelic variants and IM therapy outcome. The results were validated by sequencing.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results:<\/jats:title>\n            <jats:p>The frequency of the <jats:italic toggle=\"yes\">CYP3A4*18<\/jats:italic> allele was considerably lower in the responder\u2019s group (97.1 <jats:italic toggle=\"yes\">vs<\/jats:italic>. 100%; <jats:italic toggle=\"yes\">P<\/jats:italic>=0.036). For <jats:italic toggle=\"yes\">CYP3A5*3<\/jats:italic>, the allelic frequency was slightly higher among the IM responders (100 <jats:italic toggle=\"yes\">vs<\/jats:italic>. 99.02%) with no significant difference. Although patients heterozygous (TC) for <jats:italic toggle=\"yes\">CYP2B6*6<\/jats:italic> demonstrated a higher risk of acquiring resistance (OR 1.04; 95% CI: 0.492-2.218), differences were not significant (<jats:italic toggle=\"yes\">P<\/jats:italic>=0.909). In addition, the homozygous genotype (TT) demonstrated a lower risk of unresponsiveness (OR 0.72; 95% CI: 0.283-1.836), but associations were not significant (<jats:italic toggle=\"yes\">P<\/jats:italic>=0.491).<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Interpretation &amp; conclusions:<\/jats:title>\n            <jats:p>Our results demonstrated that <jats:italic toggle=\"yes\">CYP3A4*18<\/jats:italic> was significantly associated with IM treatment response in patients with CML in Azerbaijan, whereas rather common <jats:italic toggle=\"yes\">CYP3A5*3<\/jats:italic> was identified to have no such association.<\/jats:p>\n          <\/jats:sec>","DOI":"10.4103\/ijmr.ijmr_1103_22","type":"journal-article","created":{"date-parts":[[2023,9,12]],"date-time":"2023-09-12T04:24:08Z","timestamp":1694492648000},"page":"151-160","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":5,"title":["Association of CYP3A5*3, CYP3A4*18 &amp; CYP2B6*6 polymorphisms with imatinib treatment outcome in Azerbaijani chronic myeloid leukaemia patients"],"prefix":"10.25259","volume":"158","author":[{"given":"Chingiz","family":"Asadov","sequence":"first","affiliation":[{"name":"Department of Haematopoesis Pathology, Institute of Haematology & Transfusiology, Baku, Azerbaijan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nigar","family":"Karimova","sequence":"additional","affiliation":[{"name":"Department of Biotechnology, Genetic Resources Institute of Azerbaijan National Academy of Sciences, Baku, Azerbaijan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aypara","family":"Hasanova","sequence":"additional","affiliation":[{"name":"Department of Leukemogenesis Laboratory, Institute of Haematology & Transfusiology, Baku, Azerbaijan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bayram","family":"Bayramov","sequence":"additional","affiliation":[{"name":"Human Genetics Laboratory, Genetic Resources Institute of Azerbaijan National Academy of Sciences, Baku, Azerbaijan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aytan","family":"Shirinova","sequence":"additional","affiliation":[{"name":"Department of Haematology, Institute of Haematology & Transfusiology, Baku, Azerbaijan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zohra","family":"Alimirzoyeva","sequence":"additional","affiliation":[{"name":"Department of Haematology, Institute of Haematology & Transfusiology, Baku, Azerbaijan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"10894","published-online":{"date-parts":[[2023,9,18]]},"reference":[{"key":"R1-20241212","doi-asserted-by":"crossref","first-page":"691","DOI":"10.1002\/ajh.25792","article-title":"Chronic myeloid leukemia:2020 update on diagnosis, therapy and monitoring","volume":"95","author":"Jabbour","year":"2020","journal-title":"Am J Hematol"},{"key":"R2-20241212","doi-asserted-by":"crossref","first-page":"117","DOI":"10.3390\/cells10010117","article-title":"Chronic myeloid leukemia:A model disease of the past, present and future","volume":"10","author":"Minciacchi","year":"2021","journal-title":"Cells"},{"key":"R3-20241212","doi-asserted-by":"crossref","first-page":"395","DOI":"10.1007\/s11899-019-00543-7","article-title":"Molecular mechanisms of resistance to tyrosine kinase inhibitors","volume":"14","author":"Yaghmaie","year":"2019","journal-title":"Curr Hematol Malig Rep"},{"key":"R4-20241212","doi-asserted-by":"crossref","first-page":"1059","DOI":"10.1111\/j.1476-5381.2010.00946.x","article-title":"Participation of CYP2C8 and CYP3A4 in the N-demethylation of imatinib in human hepatic microsomes","volume":"161","author":"Nebot","year":"2010","journal-title":"Br J Pharmacol"},{"key":"R5-20241212","doi-asserted-by":"crossref","first-page":"617","DOI":"10.1007\/s40261-020-00921-7","article-title":"Effect of cytochrome P450 and ABCB1 polymorphisms on imatinib pharmacokinetics after single-dose administration to healthy subjects","volume":"40","author":"Pena","year":"2020","journal-title":"Clin Drug Investig"},{"key":"R6-20241212","doi-asserted-by":"crossref","first-page":"621","DOI":"10.1007\/s40291-017-0292-x","article-title":"Pharmacogenetics and pharmacogenomics of targeted therapeutics in chronic myeloid leukemia","volume":"21","author":"Nath","year":"2017","journal-title":"Mol Diagn Ther"},{"key":"R7-20241212","doi-asserted-by":"crossref","first-page":"383","DOI":"10.1007\/s00228-009-0772-y","article-title":"CYP3A activity influences imatinib response in patients with chronic myeloid leukemia:A pilot study on in vivo CYP3A activity","volume":"66","author":"Gr\u00e9en","year":"2010","journal-title":"Eur J Clin Pharmacol"},{"key":"R8-20241212","doi-asserted-by":"crossref","first-page":"4750","DOI":"10.1158\/1078-0432.CCR-09-0145","article-title":"Clinical relevance of a pharmacogenetic approach using multiple candidate genes to predict response and resistance to imatinib therapy in chronic myeloid leukemia","volume":"15","author":"Kim","year":"2009","journal-title":"Clin Cancer Res"},{"key":"R9-20241212","first-page":"781","article-title":"Analysis of CYP3A5*3 and CYP3A5*6 gene polymorphisms in Indian chronic myeloid leukemia patients","volume":"11","author":"Sailaja","year":"2010","journal-title":"Asian Pac J Cancer Prev"},{"key":"R10-20241212","doi-asserted-by":"crossref","first-page":"124","DOI":"10.1016\/j.ejphar.2015.08.034","article-title":"Genetic variations of hOCT1 gene and CYP3A4\/A5 genes and their association with imatinib response in chronic myeloid leukemia","volume":"765","author":"Vaidya","year":"2015","journal-title":"Eur J Pharmacol"},{"key":"R11-20241212","doi-asserted-by":"crossref","first-page":"303","DOI":"10.1007\/s40487-016-0035-x","article-title":"Impact of CYP3A4*18 and CYP3A5*3 polymorphisms on imatinib mesylate response among chronic myeloid leukemia patients in Malaysia","volume":"4","author":"Maddin","year":"2016","journal-title":"Oncol Ther"},{"key":"R12-20241212","doi-asserted-by":"crossref","first-page":"591","DOI":"10.3389\/fphar.2019.00591","article-title":"Enzymatic activities of CYP3A4 allelic variants on quinine 3-hydroxylation in vitro","volume":"10","author":"Zhou","year":"2019","journal-title":"Front Pharmacol"},{"key":"R13-20241212","doi-asserted-by":"crossref","first-page":"24","DOI":"10.3389\/fgene.2013.00024","article-title":"Pharmacogenetics of cytochrome P450 2B6 (CYP2B6):Advances on polymorphisms, mechanisms, and clinical relevance","volume":"4","author":"Zanger","year":"2013","journal-title":"Front Genet"},{"key":"R14-20241212","doi-asserted-by":"crossref","first-page":"919","DOI":"10.1016\/j.leukres.2008.11.014","article-title":"Association of CYP2B6 G15631T polymorphism with acute leukemia susceptibility","volume":"33","author":"Berk\u00f6z","year":"2009","journal-title":"Leuk Res"},{"key":"R15-20241212","doi-asserted-by":"crossref","first-page":"e88879","DOI":"10.1371\/journal.pone.0088879","article-title":"The G(5)(1)(6)T CYP2B6 germline polymorphism affects the risk of acute myeloid leukemia and is associated with specific chromosomal abnormalities","volume":"9","author":"Daraki","year":"2014","journal-title":"PLoS One"},{"key":"R16-20241212","doi-asserted-by":"crossref","first-page":"e1162","DOI":"10.1002\/mgg3.1162","article-title":"Association between CYP2B6 polymorphism and acute leukemia in a Han population of Northwest China","volume":"8","author":"Yu","year":"2020","journal-title":"Mol Genet Genomic Med"},{"key":"R17-20241212","doi-asserted-by":"crossref","first-page":"966","DOI":"10.1038\/s41375-020-0776-2","article-title":"European LeukemiaNet 2020 recommendations for treating chronic myeloid leukemia","volume":"34","author":"Hochhaus","year":"2020","journal-title":"Leukemia"},{"key":"R18-20241212","doi-asserted-by":"crossref","first-page":"iv261","DOI":"10.1093\/annonc\/mdy159","article-title":"Chronic myeloid leukaemia:ESMO clinical practice guidelines for diagnosis, treatment and follow-up","volume":"29","author":"Hochhaus","year":"2018","journal-title":"Ann Oncol"},{"key":"R19-20241212","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1016\/bs.acr.2018.02.003","article-title":"Acquired resistance to drugs targeting tyrosine kinases","volume":"138","author":"Rosenzweig","year":"2018","journal-title":"Adv Cancer Res"},{"key":"R20-20241212","doi-asserted-by":"crossref","first-page":"731","DOI":"10.1038\/jhg.2010.98","article-title":"Influence of CYP3A5 and drug transporter polymorphisms on imatinib trough concentration and clinical response among patients with chronic phase chronic myeloid leukemia","volume":"55","author":"Takahashi","year":"2010","journal-title":"J Hum Genet"},{"key":"R21-20241212","doi-asserted-by":"crossref","first-page":"756","DOI":"10.1093\/annonc\/mds532","article-title":"Influence of enzyme and transporter polymorphisms on trough imatinib concentration and clinical response in chronic myeloid leukemia patients","volume":"24","author":"Seong","year":"2013","journal-title":"Ann Oncol"},{"key":"R22-20241212","doi-asserted-by":"crossref","first-page":"1554","DOI":"10.1002\/jcph.953","article-title":"Population pharmacokinetics of imatinib in Nigerians with chronic myeloid leukemia:Clinical implications for dosing and resistance","volume":"57","author":"Adeagbo","year":"2017","journal-title":"J Clin Pharmacol"},{"key":"R23-20241212","doi-asserted-by":"crossref","first-page":"1416","DOI":"10.5114\/aoms.2018.73538","article-title":"The significance of enzyme and transporter polymorphisms for imatinib plasma levels and achieving an optimal response in chronic myeloid leukemia patients","volume":"14","author":"Belohlavkova","year":"2018","journal-title":"Arch Med Sci"},{"key":"R24-20241212","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1179\/1607845412Y.0000000067","article-title":"Do SLCO1B3 (T334G) and CYP3A5*3 polymorphisms affect response in Egyptian chronic myeloid leukemia patients receiving imatinib therapy?","volume":"18","author":"Bedewy","year":"2013","journal-title":"Hematology"},{"key":"R25-20241212","doi-asserted-by":"crossref","first-page":"3788","DOI":"10.1182\/blood.V120.21.3788.3788","article-title":"Association between CYP3A4 polymorphisms, trough imatinib plasma concentration and cytogenetic response in chronic phase chronic myeloid leukemia (CML-CP)","volume":"120","author":"Gota","year":"2012","journal-title":"Blood"},{"key":"R26-20241212","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1016\/j.cccn.2004.11.005","article-title":"CYP3A5*3 and CYP3A4*18 single nucleotide polymorphisms in a Chinese population","volume":"353","author":"Hu","year":"2005","journal-title":"Clin Chim Acta"},{"key":"R27-20241212","doi-asserted-by":"crossref","first-page":"1184","DOI":"10.1089\/gtmb.2012.0095","article-title":"Cytochrome P450 (CYP3A4*18) and glutathione-S-transferase (GSTP1) polymorphisms in a healthy Tunisian population","volume":"16","author":"Zaied","year":"2012","journal-title":"Genet Test Mol Biomarkers"},{"key":"R28-20241212","first-page":"1","article-title":"CYP3A4*18 and CYP3A5*3 single nucleotide polymorphisms in an Azerbaijani population","volume":"8","author":"Karimova","year":"2022","journal-title":"Polymorphism"},{"key":"R29-20241212","doi-asserted-by":"crossref","first-page":"3891","DOI":"10.1007\/s11033-014-3256-9","article-title":"Allele and genotype frequencies of CYP2B6 in a Turkish population","volume":"41","author":"Yuce-Artun","year":"2014","journal-title":"Mol Biol Rep"},{"key":"R30-20241212","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1517\/phgs.5.3.305.29827","article-title":"57 varieties:The human cytochromes P450","volume":"5","author":"Lewis","year":"2004","journal-title":"Pharmacogenomics"},{"key":"R31-20241212","doi-asserted-by":"crossref","first-page":"782","DOI":"10.1007\/s12032-013-0782-6","article-title":"Functional polymorphism of CYP2B6 G15631T is associated with hematologic and cytogenetic response in chronic myeloid leukemia patients treated with imatinib","volume":"31","author":"Kassogue","year":"2014","journal-title":"Med Oncol"}],"container-title":["Indian Journal of Medical Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.lww.com\/10.4103\/ijmr.ijmr_1103_22","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,7,2]],"date-time":"2025-07-02T23:06:41Z","timestamp":1751497601000},"score":1,"resource":{"primary":{"URL":"https:\/\/ijmr.org.in\/association-of-cyp3a53-cyp3a418-cyp2b66-polymorphisms-with-imatinib-treatment-outcome-in-azerbaijani-chronic-myeloid-leukaemia-patients\/"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,8]]},"references-count":31,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2023]]}},"URL":"https:\/\/doi.org\/10.4103\/ijmr.ijmr_1103_22","relation":{},"ISSN":["0971-5916","0975-9174"],"issn-type":[{"type":"print","value":"0971-5916"},{"type":"electronic","value":"0975-9174"}],"subject":[],"published":{"date-parts":[[2023,8]]},"assertion":[{"value":"2022-05-13","name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}}]}}