{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T10:01:36Z","timestamp":1753869696163,"version":"3.41.2"},"reference-count":36,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2021,2,18]],"date-time":"2021-02-18T00:00:00Z","timestamp":1613606400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Molec Gen &amp;amp; Gen Med"],"published-print":{"date-parts":[[2021,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Cytochrome P450 (CYP2B6) is an important enzyme that metabolizes about 3.0% of therapeutic drugs.\u00a0Drugs metabolized mainly by CYP2B6 include artemisinin, bupropion, cyclophosphamide, efavirenz, ketamine, and methadone.\u00a0The genetic polymorphisms in the <jats:italic>CYP2B6<\/jats:italic> gene have earlier been studied in many populations, but the data are lacking for the Pakistani population. This research study aimed to determine the frequencies of the three of the most important variant alleles and genotypes of the <jats:italic>CYP2B6<\/jats:italic> gene in the Pakistani population.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Blood was withdrawn from healthy volunteers after taking informed consent. DNA was extracted using commercial kits, and allelic and genotype frequencies were determined after PCR amplification followed by restriction fragment length polymorphism (RFLP) and gel electrophoresis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Our results show a minor allele frequency of 33.8% for <jats:italic>CYP2B6*6<\/jats:italic>, 25.8% for <jats:italic>CYP2B6*4<\/jats:italic>, 6.5% for <jats:italic>CYP2B6*3<\/jats:italic>, whereas wild\u2010type genotype frequency was 48.57% for <jats:italic>CYP2B6*6<\/jats:italic>, 59.79% for <jats:italic>CYP2B6*4<\/jats:italic>, and 90.20% for <jats:italic>CYP2B6*3<\/jats:italic>. A significant interethnic variation was also observed.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Our results suggest that the frequency of poor metabolizers of CYP2B6, especially *6 variant, is significant enough in the Pakistani population to be given an important consideration when drugs metabolized by this enzyme are prescribed.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mgg3.1527","type":"journal-article","created":{"date-parts":[[2021,2,20]],"date-time":"2021-02-20T19:10:53Z","timestamp":1613848253000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Allelic and genotype frequencies of major CYP2B6 polymorphisms in the Pakistani population"],"prefix":"10.1002","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1560-7588","authenticated-orcid":false,"given":"Sagheer","family":"Ahmed","sequence":"first","affiliation":[{"name":"Department of Basic Medical Sciences Shifa College of Pharmaceutical Sciences Shifa Tameer\u2010e\u2010Millat University Islamabad Pakistan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Saeed","family":"Khan","sequence":"additional","affiliation":[{"name":"Dow International Medical College Dow University of Health Sciences Karachi Pakistan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kholood","family":"Janjua","sequence":"additional","affiliation":[{"name":"Shifa Clinical Research Center Shifa International Hospital Islamabad Pakistan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Imran","family":"Imran","sequence":"additional","affiliation":[{"name":"Department of Pharmacology Faculty of Pharmacy Bahauddin Zakariya University Multan Pakistan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Arif Ullah","family":"Khan","sequence":"additional","affiliation":[{"name":"Riphah Institute of Pharmaceutical Sciences Riphah International University Islamabad Pakistan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2021,2,18]]},"reference":[{"issue":"4","key":"e_1_2_9_2_1","first-page":"13","article-title":"Frequencies of cytochrome P450 2B6 and 2C8 allelic variants in the Mozambican population","volume":"20","author":"Arnaldo P.","year":"2013","journal-title":"The Malaysian Journal of Medical Sciences"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.2174\/157016212803901338"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature15393"},{"issue":"23","key":"e_1_2_9_5_1","first-page":"5629","article-title":"Differential activation of cyclophosphamide and ifosfamide by cytochromes P\u2010450 2B and 3A in human liver microsomes","volume":"53","author":"Chang T. K.","year":"1993","journal-title":"Cancer Research"},{"issue":"8","key":"e_1_2_9_6_1","first-page":"985","article-title":"Human cytochrome P4502B6: Interindividual hepatic expression, substrate specificity, and role in procarcinogen activation","volume":"25","author":"Code E. L.","year":"1997","journal-title":"Drug Metabolism and Disposition"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2125.2002.01614.x"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.2217\/14622416.8.6.547"},{"issue":"3","key":"e_1_2_9_9_1","first-page":"1253","article-title":"Further characterization of the expression in liver and catalytic activity of CYP2B6","volume":"286","author":"Ekins S.","year":"1998","journal-title":"Journal of Pharmacology and Experimental Therapeutics"},{"issue":"10","key":"e_1_2_9_10_1","first-page":"1222","article-title":"Validation of bupropion hydroxylation as a selective marker of human cytochrome P450 2B6 catalytic activity","volume":"28","author":"Faucette S. R.","year":"2000","journal-title":"Drug Metabolism and Disposition"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1124\/dmd.115.064352"},{"issue":"4","key":"e_1_2_9_12_1","first-page":"533","article-title":"Role of CYP2B6 and CYP3A4 in the in vitro N\u2010dechloroethylation of (R)\u2010 and (S)\u2010ifosfamide in human liver microsomes","volume":"27","author":"Granvil C. P.","year":"1999","journal-title":"Drug Metabolism and Disposition"},{"issue":"10","key":"e_1_2_9_13_1","first-page":"1176","article-title":"CYP2B6 mediates the in vitro hydroxylation of bupropion: Potential drug interactions with other antidepressants","volume":"28","author":"Hesse L. M.","year":"2000","journal-title":"Drug Metabolism and Disposition"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1097\/00008571-200111000-00007"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.107.133306"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.103.054866"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1097\/00008571-200107000-00004"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1097\/00008571-200211000-00007"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/18.1.189"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.2174\/138920009789895534"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00228-007-0412-3"},{"key":"e_1_2_9_22_1","unstructured":"Pakistan Bureau of Statistics. (2017).Block Wise Provisional Summary Results of 6th Population & Housing Census. [As on January 03 2018].http:\/\/www.pbs.gov.pk\/content\/block\u2010wise\u2010provisional\u2010summary\u2010results\u20106th\u2010population\u2010housing\u2010census\u20102017\u2010january\u201003\u20102018"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0304-4165(02)00483-X"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2826.1999.00371.x"},{"issue":"6","key":"e_1_2_9_25_1","first-page":"655","article-title":"Development of a substrate\u2010activity based approach to identify the major human liver P\u2010450 catalysts of cyclophosphamide and ifosfamide activation based on cDNA\u2010expressed activities and liver microsomal P\u2010450 profiles","volume":"27","author":"Roy P.","year":"1999","journal-title":"Drug Metabolism and Disposition"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1124\/mol.63.1.96"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.4238\/2015.December.11.6"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0009-9236(03)00092-4"},{"issue":"4","key":"e_1_2_9_29_1","first-page":"517","article-title":"Monospecific antipeptide antibody to cytochrome P\u2010450 2B6","volume":"27","author":"Stresser D. M.","year":"1999","journal-title":"Drug Metabolism and Disposition"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.274.10.6043"},{"volume-title":"Pakistan in pictures","year":"2003","author":"Taus\u2010Bolstad S.","key":"e_1_2_9_31_1"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1515\/dmdi-2012-0027"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.2174\/138920008785821710"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.1021\/bi00444a029"},{"issue":"10","key":"e_1_2_9_35_1","first-page":"685","article-title":"Genetic variability of CYP2B6 polymorphisms in southeast Iranian population: Implications for malaria and HIV\/AIDS treatment","volume":"17","author":"Zakeri S.","year":"2014","journal-title":"Archives of Iranian Medicine"},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.3389\/fgene.2013.00024"},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pharmthera.2012.12.007"}],"container-title":["Molecular Genetics &amp; Genomic Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/mgg3.1527","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/mgg3.1527","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/mgg3.1527","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,29]],"date-time":"2023-08-29T18:15:46Z","timestamp":1693332946000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/mgg3.1527"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,2,18]]},"references-count":36,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2021,3]]}},"alternative-id":["10.1002\/mgg3.1527"],"URL":"https:\/\/doi.org\/10.1002\/mgg3.1527","archive":["Portico"],"relation":{},"ISSN":["2324-9269","2324-9269"],"issn-type":[{"type":"print","value":"2324-9269"},{"type":"electronic","value":"2324-9269"}],"subject":[],"published":{"date-parts":[[2021,2,18]]},"assertion":[{"value":"2020-07-10","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-09-25","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-02-18","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e1527"}}