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

Pharmacogenetics and Genomics

Volumn 18, Issue 5, 2008, Pages 390-402

  Hung, Chin Chuan ^a   Chen, Chih Chuan ^b   Lin, Chun Jung ^a   Liou, Horng Huei ^a,b  

^a NATIONAL TAIWAN UNIVERSITY   (Taiwan)

^b NATIONAL TAIWAN UNIVERSITY HOSPITAL   (Taiwan)

Author keywords

ABCB1; Epilepsy treatment outcome; Pharmacogenetic; Pharmacokinetic; Polymorphism

Indexed keywords

ANTICONVULSIVE AGENT; CALCEIN; CARBAMAZEPINE; CYCLOSPORIN A; ETIRACETAM; GABAPENTIN; GLYCOPROTEIN P; LAMOTRIGINE; PHENOBARBITAL; PHENYTOIN; RHODAMINE 123; VALPROIC ACID; VERAPAMIL;

ARTICLE; DOSE RESPONSE; DRUG TRANSPORT; EMBRYO; ENZYME SUBSTRATE; GENE SEQUENCE; GENETIC POLYMORPHISM; GENOTYPE; HAPLOTYPE; HUMAN; HUMAN CELL; PRIORITY JOURNAL; PROTEIN EXPRESSION; PROTEIN FUNCTION; SITE DIRECTED MUTAGENESIS;

ANTICONVULSANTS; BASE SEQUENCE; CELLS, CULTURED; DOSE-RESPONSE RELATIONSHIP, DRUG; DRUG RESISTANCE; EPILEPSY; FLUORESCEINS; FLUORESCENT DYES; HUMANS; P-GLYCOPROTEIN; POLYMORPHISM, SINGLE NUCLEOTIDE; PROGNOSIS; RHODAMINE 123;

EID: 42149157159     PISSN: 17446872     EISSN: 17446880     Source Type: Journal    
DOI: 10.1097/FPC.0b013e3282f85e36     Document Type: Article

References (68)

1. Juliano RL, Ling V. A surface glycoprotein modulating drug permeability in Chinese hamster ovary cell mutants. Biochim Biophys Acta 1976; 455:152-162.
2. Horio M, Gottesman MM, Pastan I. ATP-dependent transport of vinblastine in vesicles from human multidrug-resistant cells. Proc Natl Acad Sci U S A 1988; 85:3580-3584.
3. Tanigawara Y. Role of P-glycoprotein in drug disposition. Ther Drug Monit 2000; 22:137-140.
4. Rao VV, Dahlheimer JL, Bardgett ME, Snyder AZ, Finch RA, Sartorelli AC, et al. Choroid plexus epithelial expression of MDR1 P glycoprotein and multidrug resistance-associated protein contribute to the blood-cerebrospinal- fluid drug-permeability barrier. Proc Natl Acad Sci U S A 1999; 96:3900-3905.
5. Schinkel AH. The physiological function of drug-transporting P-glycoproteins. Semin Cancer Biol 1997; 8:161-170.
6. Cordon-Cardo C, O'Brien JP, Casals D, Rittman-Grauer L, Biedler JL, Melamed MR, et al. Multidrug-resistance gene (P-glycoprotein) is expressed by endothelial cells at blood-brain barrier sites. Proc Natl Acad Sci U S A 1989; 86:695-698.
7. Borst P, Evers R, Kool M, Wijnholds J. The multidrug resistance protein family. Biochim Biophys Acta 1999; 1461:347-357.
8. Marzolini C, Paus E, Buclin T, Kim RB. Polymorphisms in human MDR1 (P-glycoprotein): recent advances and clinical relevance. Clin Pharmacol Ther 2004; 75:13-33.
9. Schwab M, Eichelbaum M, Fromm MF. Genetic polymorphisms of the human MDR1 drug transporter. Annu Rev Pharmacol Toxicol 2003; 43:285-307.
10. Sakaeda T, Nakamura T, Okumura K. Pharmacogenetics of MDR1 and its impact on the pharmacokinetics and pharmacodynamics of drugs. Pharmacogenomics 2003; 4:397-410.
11. Kim RB, Leake BF, Choo EF, Dresser GK, Kubba SV, Schwarz UI, et al. Identification of functionally variant MDR1 alleles among European Americans and African Americans. Clin Pharmacol Ther 2001; 70:189-199.
12. MacDonald BK, Johnson AL, Goodridge DM, Cockerell OC, Sander JW, Shorvon SD. Factors predicting prognosis of epilepsy after presentation with seizures. Ann Neurol 2000; 48:833-841.
13. Loscher W, Potschka H. Role of multidrug transporters in pharmacoresistance to antiepileptic drugs. J Pharmacol Exp Ther 2002; 301:7-14.
14. Tishler DM, Weinberg KI, Hinton DR, Barbaro N, Annett GM, Raffel C. MDR1 gene expression in brain of patients with medically intractable epilepsy. Epilepsia 1995; 36:1-6.
15. Dombrowski SM, Desai SY, Marroni M, Cucullo L, Goodrich K, Bingaman W, et al. Overexpression of multiple drug resistance genes in endothelial cells from patients with refractory epilepsy. Epilepsia 2001; 42:1501-1506.
16. Lepper ER, Nooter K, Verweij J, Acharya MR, Figg WD, Sparreboom A. Mechanisms of resistance to anticancer drugs: the role of the polymorphic ABC transporters ABCB1 and ABCG2. Pharmacogenomics 2005; 6:115-138.
17. Pauli-Magnus C, Kroetz DL. Functional implications of genetic polymorphisms in the multidrug resistance gene MDR1 (ABCB1). Pharm Res 2004; 21:904-913.
18. Kroetz DL, Pauli-Magnus C, Hodges LM, Huang CC, Kawamoto M, Johns SJ, et al. Sequence diversity and haplotype structure in the human ABCB1 (MDR1, multidrug resistance transporter) gene. Pharmacogenetics 2003; 13:481-494.
19. Hoffmeyer S, Burk O, von Richter O, Arnold HP, Brockmoller J, Johne A, et al. Functional polymorphisms of the human multidrug-resistance gene: multiple sequence variations and correlation of one allele with P-glycoprotein expression and activity in vivo. Proc Natl Acad Sci U S A 2000; 97:3473-3478.
20. Nakamura T, Sakaeda T, Horinouchi M, Tamura T, Aoyama N, Shirakawa T, et al. Effect of the mutation (C3435T) at exon 26 of the MDR1 gene on expression level of MDR1 messenger ribonucleic acid in duodenal enterocytes of healthy Japanese subjects. Clin Pharmacol Ther 2002; 71:297-303.
21. Siegmund W, Ludwig K, Giessmann T, Dazert P, Schroeder E, Sperker B, et al. The effects of the human MDR1 genotype on the expression of duodenal P-glycoprotein and disposition of the probe drug talinolol. Clin Pharmacol Ther 2002; 72:572-583.
22. Hitzl M, Drescher S, van der Kuip H, Schaffeler E, Fischer J, Schwab M, et al. The C3435T mutation in the human MDR1 gene is associated with altered efflux of the P-glycoprotein substrate rhodamine 123 from CD56 + natural killer cells. Pharmacogenetics 2001; 11:293-298.
23. Oselin K, Gerloff T, Mrozikiewicz PM, Pahkla R, Roots I. MDR1 polymorphisms G2677T in exon 21 and C3435T in exon 26 fail to affect rhodamine 123 efflux in peripheral blood lymphocytes. Fundam Clin Pharmacol 2003; 17:463-469.
24. Calado RT, Falcao RP, Garcia AB, Gabellini SM, Zago MA, Franco RF. Influence of functional MDR1 gene polymorphisms on P-glycoprotein activity in CD34+ hematopoietic stem cells. Haematologica 2002; 87:564-568.
25. Saitoh A, Singh KK, Powell CA, Fenton T, Fletcher CV, Brundage R, et al. An MDR1-3435 variant is associated with higher plasma nelfinavir levels and more rapid virologic response in HIV-1 infected children. Aids 2005; 19:371-380.
26. Bonhomme-Faivre L, Devocelle A, Saliba F, Chatled S, Maccario J, Farinotti R, et al. MDR-1 C3435T polymorphism influences cyclosporine a dose requirement in liver-transplant recipients. Transplantation 2004; 78:21-25.
27. Nasi M, Borghi V, Pinti M, Bellodi C, Lugli E, Maffei S, et al. MDR1 C3435T genetic polymorphism does not influence the response to antiretroviral therapy in drug-naive HIV-positive patients. Aids 2003; 17:1696-1698.
28. Fellay J, Marzolini C, Meaden ER, Back DJ, Buclin T, Chave JP, et al. Response to antiretroviral treatment in HIV-1-infected individuals with allelic variants of the multidrug resistance transporter 1: a pharmacogenetics study. Lancet 2002; 359:30-36.
29. Drescher S, Schaeffeler E, Hitzl M, Hofmann U, Schwab M, Brinkmann U, et al. MDR1 gene polymorphisms and disposition of the P-glycoprotein substrate fexofenadine. Br J Clin Pharmacol 2002; 53:526-534.
30. von Ahsen N, Richter M, Grupp C, Ringe B, Oellerich M, Armstrong VW. No influence of the MDR-1 C3435T polymorphism or a CYP3A4 promoter polymorphism (CYP3A4-V allele) on dose-adjusted cyclosporin A trough concentrations or rejection incidence in stable renal transplant recipients. Clin Chem 2001; 47:1048-1052.
31. Sakaeda T, Nakamura T, Horinouchi M, Kakumoto M, Ohmoto N, Sakai T, et al. MDR1 genotype-related pharmacokinetics of digoxin after single oral administration in healthy Japanese subjects. Pharm Res 2001; 18:1400-1404.
32. Anglicheau D, Verstuyft C, Laurent-Puig P, Becquemont L, Schlageter MH, Cassinat B, et al. Association of the multidrug resistance-1 gene single-nucleotide polymorphisms with the tacrolimus dose requirements in renal transplant recipients. J Am Soc Nephrol 2003; 14:1889-1896.
33. Johne A, Kopke K, Gerloff T, Mai I, Rietbrock S, Meisel C, et al. Modulation of steady-state kinetics of digoxin by haplotypes of the P-glycoprotein MDR1 gene. Clin Pharmacol Ther 2002; 72:584-594.
34. Illmer T, Schuler US, Thiede C, Schwarz UI, Kim RB, Gotthard S, et al. MDR1 gene polymorphisms affect therapy outcome in acute myeloid leukemia patients. Cancer Res 2002; 62:4955-4962.
35. Goto M, Masuda S, Saito H, Uemoto S, Kiuchi T, Tanaka K, et al. C3435T polymorphism in the MDR1 gene affects the enterocyte expression level of CYP3A4 rather than Pgp in recipients of living-donor liver transplantation. Pharmacogenetics 2002; 12:451-457.
36. Mathijssen RH, Marsh S, Karlsson MO, Xie R, Baker SD, Verweij J, et al. Irinotecan pathway genotype analysis to predict pharmacokinetics. Clin Cancer Res 2003; 9:3246-3253.
37. Morita N, Yasumori T, Nakayama K. Human MDR1 polymorphism: G2677T/A and C3435T have no effect on MDR1 transport activities. Biochem Pharmacol 2003; 65:1843-1852.
38. Cascorbi I, Gerloff T, Johne A, Meisel C, Hoffmeyer S, Schwab M, et al. Frequency of single nucleotide polymorphisms in the P-glycoprotein drug transporter MDR1 gene in white subjects. Clin Pharmacol Ther 2001; 69:169-174.
39. Siddiqui A, Kerb R, Weale ME, Brinkmann U, Smith A, Goldstein DB, et al. Association of multidrug resistance in epilepsy with a polymorphism in the drug-transporter gene ABCB1. N Engl J Med 2003; 348:1442-1448.
40. Zimprich F, Sunder-Plassmann R, Stogmann E, Gleiss A, Dal-Bianco A, Zimprich A, et al. Association of an ABCB1 gene haplotype with pharmacoresistance in temporal lobe epilepsy. Neurology 2004; 63:1087-1089.
41. Hung CC, Tai JJ, Lin CJ, Lee MJ, Liou HH. Complex haplotypic effects of the ABCB1 gene on epilepsy treatment response. Pharmacogenomics 2005; 6:411-417.
42. Seo T, Ishitsu T, Ueda N, Nakada N, Yurube K, Ueda K, et al. ABCB1 polymorphisms influence the response to antiepileptic drugs in Japanese epilepsy patients. Pharmacogenomics 2006; 7:551-561.
43. Kwan P, Baum L, Wong V, Ng PW, Lui CH, Sin NC, et al. Association between ABCB1 C3435T polymorphism and drug-resistant epilepsy in Han Chinese. Epilepsy Behav 2007; 11:112-117.
44. Tan NC, Heron SE, Scheffer IE, Pelekanos JT, McMahon JM, Vears DF, et al. Failure to confirm association of a polymorphism in ABCB1 with multidrug-resistant epilepsy. Neurology 2004; 63:1090-1092.
45. Leschziner GD, Andrew T, Leach JP, Chadwick D, Coffey AJ, Balding DJ, et al. Common ABCB1 polymorphisms are not associated with multidrug resistance in epilepsy using a gene-wide tagging approach. Pharmacogenet Genomics 2007; 17:217-220.
46. Shahwan A, Murphy K, Doherty C, Cavalleri GL, Muckian C, Dicker P, et al. The controversial association of ABCB1 polymorphisms in refractory epilepsy: an analysis of multiple SNPs in an Irish population. Epilepsy Res 2007; 73:192-198.
47. Kim DW, Kim M, Lee SK, Kang R, Lee SY. Lack of association between C3435T nucleotide MDR1 genetic polymorphism and multidrug-resistant epilepsy. Seizure 2006; 15:344-347.
48. Sills GJ, Mohanraj R, Butler E, McCrindle S, Collier L, Wilson EA, et al. Lack of association between the C3435T polymorphism in the human multidrug resistance (MDR1) gene and response to antiepileptic drug treatment. Epilepsia 2005; 46:643-647.
49. Leschziner G, Jorgensen AL, Andrew T, Pirmohamed M, Williamson PR, Marson AG, et al. Clinical factors and ABCB1 polymorphisms in prediction of antiepileptic drug response: a prospective cohort study. Lancet Neurol 2006; 5:668-676.
50. Fromm MF. The influence of MDR1 polymorphisms on P-glycoprotein expression and function in humans. Adv Drug Deliv Rev 2002; 54:1295-1310.
51. Scheffer GL, Kool M, Heijn M, de Haas M, Pijnenborg AC, Wijnholds J, et al. Specific detection of multidrug resistance proteins MRP1, MRP2, MRP3, MRP5, and MDR3 P-glycoprotein with a panel of monoclonal antibodies. Cancer Res 2000; 60:5269-5277.
52. Julien M, Gros P. Nucleotide-induced conformational changes in P-glycoprotein and in nucleotide binding site mutants monitored by trypsin sensitivity. Biochemistry 2000; 39:4559-4568.
53. Demeule M, Jodoin J, Gingras D, Beliveau R. P-glycoprotein is localized in caveolae in resistant cells and in brain capillaries. FEBS Lett 2000; 466:219-224.
54. Kimchi-Sarfaty C, Gribar JJ, Gottesman MM. Functional characterization of coding polymorphisms in the human MDR1 gene using a vaccinia virus expression system. Mol Pharmacol 2002; 62:1-6.
55. Kimchi-Sarfaty C, Oh JM, Kim IW, Sauna ZE, Calcagno AM, Ambudkar SV, et al. A 'silent' polymorphism in the MDR1 gene changes substrate specificity. Science 2007; 315:525-528.
56. Chinn LW, Kroetz DL. ABCB1 pharmacogenetics: progress, pitfalls, and promise. Clin Pharmacol Ther 2007; 81:265-269.
57. Weiss J, Kerpen CJ, Lindenmaier H, Dormann SM, Haefeli WE. Interaction of antiepileptic drugs with human P-glycoprotein in vitro. J Pharmacol Exp Ther 2003; 307:262-267.
58. Kwan P, Brodie MJ. Potential role of drug transporters in the pathogenesis of medically intractable epilepsy. Epilepsia 2005; 46:224-235.
59. Potschka H, Baltes S, Loscher W. Inhibition of multidrug transporters by verapamil or probenecid does not alter blood-brain barrier penetration of levetiracetam in rats. Epilepsy Res 2004; 58:85-91.
60. Owen A, Pirmohamed M, Tettey JN, Morgan P, Chadwick D, Park BK. Carbamazepine is not a substrate for P-glycoprotein. Br J Clin Pharmacol 2001; 51:345-349.
61. Iannetti P, Spalice A, Parisi P. Calcium-channel blocker verapamil administration in prolonged and refractory status epilepticus. Epilepsia 2005; 46:967-969.
62. Summers MA, Moore JL, McAuley JW. Use of verapamil as a potential P-glycoprotein inhibitor in a patient with refractory epilepsy. Ann Pharmacother 2004; 38:1631-1634.
63. Loscher W. Drug transporters in the epileptic brain. Epilepsia 2007; 48 (Suppl 1):8-13.
64. Meyer FP, Banditt P, Schubert A, Schoche J. Lamotrigine concentrations in human serum, brain tissue, and tumor tissue. Epilepsia 1999; 40:68-73.
65. Sironi VA, Cabrini G, Porro MG, Ravagnati L, Marossero F. Antiepileptic drug distribution in cerebral cortex, ammon's horn, and amygdala in man. J Neurosurg 1980; 52:686-692.
66. Baltes S, Gastens AM, Fedrowitz M, Potschka H, Kaever V, Loscher W. Differences in the transport of the antiepileptic drugs phenytoin, levetiracetam and carbamazepine by human and mouse P-glycoprotein. Neuropharmacology 2007; 52:333-346.
67. Salama NN, Yang Z, Bui T, Ho RJ. MDR1 haplotypes significantly minimize intracellular uptake and transcellular P-gp substrate transport in recombinant LLC-PK1 cells. J Pharm Sci 2006; 95:2293-2308.
68. Schaefer M, Roots I, Gerloff T. In-vitro transport characteristics discriminate wild-type ABCB1 (MDR1) from ALA893SER and ALA893THR polymorphisms. Pharmacogenet Genomics 2006; 16:855-861.