Functional evaluation of polymorphisms in the human ABCB1 gene and the impact on clinical responses of antiepileptic drugs

Pharmacogenetics and Genomics
Chin-Chuan HungHorng-Huei Liou

Abstract

The ABCB1 haplotype combinations have been demonstrated to be associated with epilepsy treatment outcomes. The aim of this study is to investigate whether ABCB1 haplotype combinations would affect P-glycoprotein (Pgp) function and impact the clinical responses of antiepileptic drugs (AEDs). Transport of substrate rhodamine 123 and calcein-AM by human Pgp carrying 12 haplotype combinations of 1236C>T, 2677G>T/A and 3435C>T were assayed in the absence and presence of known inhibitors and AEDs. The inhibitory potency of the tested drugs from the dose-response relationships was cyclosporin A>verapamil> phenytoin> carbamazepine> lamotrigine>phenobarbital>valproic acid, levetiracetam, gabapentin. The silent polymorphisms combination (1236T-3435T) and triple haplotypes (1236T-2677A/T-3435T) resulted in profoundly less effective inhibition against substrates with significantly lower intracellular substrate concentration. These results confirmed that ABCB1 polymorphisms were associated with clinical responses of AEDs. Our findings demonstrated that human ABCB1 polymorphisms may alter the interactions between Pgp and substrates, and provided functional evidence for ABCB1 haplotypes-associated epilepsy treatment responses.

References

Nov 11, 1976·Biochimica Et Biophysica Acta·R L Juliano, V Ling
Jan 1, 1989·Proceedings of the National Academy of Sciences of the United States of America·C Cordon-CardoJ R Bertino
May 1, 1988·Proceedings of the National Academy of Sciences of the United States of America·M HorioI Pastan
May 1, 1980·Journal of Neurosurgery·V A SironiF Marossero
Jun 1, 1997·Seminars in Cancer Biology·A H Schinkel
Mar 31, 1999·Proceedings of the National Academy of Sciences of the United States of America·V V RaoD Piwnica-Worms
Dec 3, 1999·Biochimica Et Biophysica Acta·P BorstJ Wijnholds
Feb 25, 2000·Therapeutic Drug Monitoring·Y Tanigawara
Apr 25, 2001·British Journal of Clinical Pharmacology·A OwenB K Park
Aug 15, 2001·Clinical Pharmacology and Therapeutics·R B KimG R Wilkinson
Mar 22, 2002·The Journal of Pharmacology and Experimental Therapeutics·Wolfgang Löscher, Heidrun Potschka
May 8, 2002·British Journal of Clinical Pharmacology·Siegfried DrescherMartin F Fromm
Jun 18, 2002·Molecular Pharmacology·Chava Kimchi-SarfatyMichael M Gottesman
Oct 3, 2002·Annual Review of Pharmacology and Toxicology·Matthias SchwabMartin F Fromm
Oct 31, 2002·Advanced Drug Delivery Reviews·Martin F Fromm
Nov 12, 2002·Clinical Pharmacology and Therapeutics·Andreas JohneIvar Roots
Apr 11, 2003·The New England Journal of Medicine·Asra SiddiquiSanjay M Sisodiya
Jun 5, 2003·Biochemical Pharmacology·Naomi MoritaKazuo Nakayama
Jul 2, 2003·Pharmacogenomics·Toshiyuki SakaedaKatsuhiko Okumura
Aug 2, 2003·Pharmacogenetics·Deanna L KroetzUNKNOWN Pharmacogenetics of Membrane Transporters Investigators
Sep 5, 2003·The Journal of Pharmacology and Experimental Therapeutics·Johanna WeissWalter Emil Haefeli
Jan 30, 2004·Clinical Pharmacology and Therapeutics·Catia MarzoliniRichard B Kim
Jun 24, 2004·Pharmaceutical Research·Christiane Pauli-Magnus, Deanna L Kroetz
Jul 17, 2004·Transplantation·Laurence Bonhomme-FaivreVéronique Picard
Aug 26, 2004·The Annals of Pharmacotherapy·Monica A SummersJames W McAuley
Jul 12, 2005·Pharmacogenomics·Chin-Chuan HungHorng-Huei Liou
Mar 18, 2006·Seizure : the Journal of the British Epilepsy Association·Dong Wook KimSeo-Young Lee

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Citations

Oct 2, 2012·CNS Drugs·Yumiko AkamineTsukasa Uno
May 10, 2012·Pharmacogenetics and Genomics·Caroline F ThornRuss B Altman
Apr 15, 2011·Journal of Veterinary Internal Medicine·L AlvesM Drögemüller
May 20, 2009·Pharmacogenomics·Dalia Kasperaviciūte, Sanjay M Sisodiya
Oct 20, 2011·Pharmacogenomics·Gianpiero L CavalleriNorman Delanty
May 10, 2013·Journal of Pharmaceutical Sciences·Ming-Liang LaiJin-Ding Huang
Dec 27, 2011·Advanced Drug Delivery Reviews·Chunbo ZhangLarry Baum
Mar 17, 2009·Biochimica Et Biophysica Acta·King Leung Fung, Michael M Gottesman
Jul 15, 2009·International Journal of Cancer. Journal International Du Cancer·Sung Pil HongSi Young Song
May 29, 2012·CNS Neuroscience & Therapeutics·Jian QuZhao-Qian Liu
Nov 29, 2013·Biopharmaceutics & Drug Disposition·Jun LeeXiaoyang Lu
Jul 16, 2015·International Journal of Clinical Pharmacy·Alessio ProvenzaniNatale D'Alessandro
Oct 1, 2008·Neuropharmacology·Carlos Luna-TortósWolfgang Löscher
May 16, 2015·Neurología : publicación oficial de la Sociedad Española de Neurología·I Fricke-GalindoM López-López
Jan 13, 2010·Seizure : the Journal of the British Epilepsy Association·M Blanca SánchezJuan A Armijo
Jul 20, 2016·Expert Opinion on Drug Metabolism & Toxicology·Sven C van DijkmanOscar Della Pasqua
Sep 8, 2017·Journal of Human Genetics·Miao-Miao ZhuZan-Ling Zhang
Jun 28, 2013·Asian Pacific Journal of Cancer Prevention : APJCP·Xiao-Di GongBin Jiang
Jun 22, 2016·Annals of Global Health·Judit MarsillachClement E Furlong
Mar 19, 2020·Pharmacogenetics and Genomics·Taraswi Mitra-GhoshRuss B Altman
Nov 19, 2014·International Journal of Molecular Sciences·David AbellóJorge Joven
Nov 24, 2020·Pharmacogenomics·Qingyang XiaoVolker M Lauschke
Jan 19, 2021·Expert Opinion on Drug Metabolism & Toxicology·Henrike Bruckmueller, Ingolf Cascorbi
Jan 27, 2021·International Journal of Molecular Sciences·Song GaoDong Liang

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