Nuclear receptor-mediated induction of CYP450 by antiretrovirals: Functional consequences of NR1I2 (PXR) polymorphisms and differential prevalence in whites and sub-Saharan Africans

Journal of Acquired Immune Deficiency Syndromes

Volumn 55, Issue 5, 2010, Pages 536-549

  Svärd, Jenny ^a   Spiers, J Paul ^a   Mulcahy, Fiona ^a   Hennessy, Martina ^a  

^a ST JAMES S HOSPITAL   (Ireland)

Author keywords

antiretroviral therapy; CYP450; drug interactions; HIV protease inhibitor; polymorphism; PXR

Indexed keywords

ABACAVIR; ANTIRETROVIRUS AGENT; CELL NUCLEUS RECEPTOR; CONSTITUTIVE ANDROSTANE RECEPTOR; CYTOCHROME P450 2B6; CYTOCHROME P450 3A4; DARUNAVIR; EFAVIRENZ; FOSAMPRENAVIR; LOPINAVIR; NELFINAVIR; PREGNANE X RECEPTOR; PROTEINASE INHIBITOR; RITONAVIR; SAQUINAVIR; TIPRANAVIR;

ADULT; AFRICA; ARTICLE; DRUG ACTIVITY; ETHNICITY; FEMALE; GENE INDUCTION; GENETIC VARIABILITY; HUMAN; HUMAN CELL; HUMAN IMMUNODEFICIENCY VIRUS INFECTION; LOW DRUG DOSE; MAJOR CLINICAL STUDY; MALE; PREVALENCE; PRIORITY JOURNAL; PROMOTER REGION; PROTEIN BLOOD LEVEL; PROTEIN EXPRESSION; SINGLE NUCLEOTIDE POLYMORPHISM;

ADULT; AFRICA SOUTH OF THE SAHARA; AFRICAN CONTINENTAL ANCESTRY GROUP; ANDROSTANES; ANTI-HIV AGENTS; ARYL HYDROCARBON HYDROXYLASES; CELL LINE; CYTOCHROME P-450 CYP3A; DRUG INTERACTIONS; EUROPEAN CONTINENTAL ANCESTRY GROUP; FEMALE; GENOTYPE; HEP G2 CELLS; HIV INFECTIONS; HIV PROTEASE INHIBITORS; HUMANS; MALE; MIDDLE AGED; OXIDOREDUCTASES, N-DEMETHYLATING; POLYMORPHISM, SINGLE NUCLEOTIDE; PROMOTER REGIONS, GENETIC; RECEPTORS, STEROID; REVERSE TRANSCRIPTASE INHIBITORS;

EID: 78650210692     PISSN: 15254135     EISSN: None     Source Type: Journal    
DOI: 10.1097/QAI.0b013e3181f52f0c     Document Type: Article

References (72)

1. Dooley KE, Flexner C, Andrade AS. Drug interactions involving combination antiretroviral therapy and other anti-infective agents: repercussions for resource-limited countries. J Infect Dis. 2008;7: 948-961.
2. Li T, Chen W, Chiang JY. PXR induces CYP27A1 and regulates cholesterol metabolism in the intestine. J Lipid Res. 2007;2:373-384.
3. Moreau A, Vilarem MJ, Maurel P, et al. Xenoreceptors CAR and PXR activation and consequences on lipid metabolism, glucose homeostasis, and inflammatory response. Mol Pharm. 2008;1:35-41.
4. Dussault I, Lin M, Hollister K, et al. Peptide mimetic HIV protease inhibitors are ligands for the orphan receptor SXR. J Biol Chem. 2001;36: 33309-33312.
5. Luo G, Cunningham M, Kim S, et al. CYP3A4 induction by drugs: correlation between a pregnane X receptor reporter gene assay and CYP3A4 expression in human hepatocytes. Drug Metab Dispos. 2002;7: 795-804.
6. Huang L, Wring SA, Woolley JL, et al. Induction of P-glycoprotein and cytochrome P450 3A by HIV protease inhibitors. Drug Metab Dispos. 2001;5:754-760.
7. Gupta A, Mugundu GM, Desai PB, et al. Intestinal human colon adenocarcinoma cell line LS180 is an excellent model to study pregnane X receptor, but not constitutive androstane receptor, mediated CYP3A4 and multidrug resistance transporter 1 induction: studies with anti-human immunodeficiency virus protease inhibitors. Drug Metab Dispos. 2008;6: 1172-1180.
8. Hariparsad N, Nallani SC, Sane RS, et al. Induction of CYP3A4 by efavirenz in primary human hepatocytes: comparison with rifampin and phenobarbital. J Clin Pharmacol. 2004;11:1273-1281.
9. Fellay J, Marzolini C, Decosterd L, et al. Variations of CYP3A activity induced by antiretroviral treatment in HIV-1 infected patients. Eur J Clin Pharmacol. 2005;12:865-873.
10. Zhang J, Kuehl P, Green ED, et al. The human pregnane X receptor: genomic structure and identification and functional characterization of natural allelic variants. Pharmacogenetics. 2001;7:555-572.
11. King CR, Xiao M, Yu J, et al. Identification of NR1I2 genetic variation using resequencing. Eur J Clin Pharmacol. 2007;6:547-554.
12. Lamba J, Lamba V, Strom S, et al. Novel single nucleotide polymorphisms in the promoter and intron 1 of human pregnane X receptor/NR1I2 and their association with CYP3A4 expression. Drug Metab Dispos. 2008;1: 169-181.
13. Hustert E, Zibat A, Presecan-Siedel E, et al. Natural protein variants of pregnane X receptor with altered transactivation activity toward CYP3A4. Drug Metab Dispos. 2001;11:1454-1459.
14. Siccardi M, D'Avolio A, Baietto L, et al. Association of a single-nucleotide polymorphism in the pregnane X receptor (PXR 63396C-.T) with reduced concentrations of unboosted atazanavir. Clin Infect Dis. 2008;9:1222-1225.
15. Haas DW, Ribaudo HJ, Kim RB, et al. Pharmacogenetics of efavirenz and central nervous system side effects: an Adult AIDS Clinical Trials Group study. AIDS. 2004;18:2391-2400.
16. Saitoh A, Singh KK, Powell CA, 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;4:371-380.
17. Fellay J, Marzolini C, Meaden ER, 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;9300:30-36.
18. Haas DW, Smeaton LM, Shafer RW, et al. Pharmacogenetics of long-term responses to antiretroviral regimens containing eavirenz and/or nelfinavir: an Adult Aids Clinical Trials Group Study. J Infect Dis. 2005;11: 1931-1942.
19. Rodriguez-Novoa S, Barreiro P, Rendon A, et al. Influence of 516G.T polymorphisms at the gene encoding the CYP450-2B6 isoenzyme on efavirenz plasma concentrations in HIV-infected subjects. Clin Infect Dis. 2005;9:1358-1361.
20. Rotger M, Colombo S, Furrer H, et al. Influence of CYP2B6 polymorphism on plasma and intracellular concentrations and toxicity of efavirenz and nevirapine in HIV-infected patients. Pharmacogenet Genomics. 2005;1:1-5.
21. Ikeda S, Kurose K, Jinno H, et al. Functional analysis of four naturally occurring variants of human constitutive androstane receptor. Mol Genet Metab. 2005;1-2:314-319.
22. Dring MM, Goulding CA, Trimble VI, et al. The pregnane X receptor locus is associated with susceptibility to inflammatory bowel disease. Gastroenterology. 2006;2:341-348.
23. Roy JN, Barama A, Poirier C, et al. Cyp3A4, Cyp3A5, and MDR-1 genetic influences on tacrolimus pharmacokinetics in renal transplant recipients. Pharmacogenet Genomics. 2006;9:659-665.
24. Lang T, Klein K, Fischer J, et al. Extensive genetic polymorphism in the human CYP2B6 gene with impact on expression and function in human liver. Pharmacogenetics. 2001;5:399-415.
25. von HN, Babacan E, Lennemann T, et al. The steady-state pharmaco-kinetics of atazanavir/ritonavir in HIV-1-infected adult outpatients is not affected by gender-related co-factors. J Antimicrob Chemother. 2008;3: 579-582.
26. Sekar VJ, Lefebvre E, De PE, et al. Pharmacokinetic interaction between darunavir boosted with ritonavir and omeprazole or ranitidine in human immunodeficiency virus-negative healthy volunteers. Antimicrob Agents Chemother. 2007;3:958-961.
27. Luber AD, Brower R, Kim D, et al. Steady-state pharmacokinetics of once-daily fosamprenavir/ritonavir and atazanavir/ritonavir alone and in combination with 20 mg omeprazole in healthy volunteers. HIV Med. 2007;7:457-464.
28. Saah AJ, Winchell GA, Nessly ML, et al. Pharmacokinetic profile and tolerability of indinavir-ritonavir combinations in healthy volunteers. Antimicrob Agents Chemother. 2001;10:2710-2715.
29. Klein CE, Chiu YL, Cai Y, et al. Effects of acid-reducing agents on the pharmacokinetics of lopinavir/ritonavir and ritonavir-boosted atazanavir. J Clin Pharmacol. 2008;5:553-562.
30. Justesen US, Hansen IM, Andersen AB, et al. The long-term pharmacokinetics and safety of adding low-dose ritonavir to a nelfinavir 1,250 mg twice-daily regimen in HIV-infected patients. HIV Med. 2005;5: 334-340.
31. Kearney BP, Mathias A, Mittan A, et al. Pharmacokinetics and safety of tenofovir disoproxil fumarate on coadministration with lopinavir/ritonavir. J Acquir Immune Defic Syndr. 2006;3:278-283.
32. Bittner B, Riek M, Holmes B, et al. Saquinavir 500 mg film-coated tablets demonstrate bioequivalence to saquinavir 200 mg hard capsules when boosted with twice-daily ritonavir in healthy volunteers. Antivir Ther. 2005;7:803-810.
33. McCallister S, Valdez H, Curry K, et al. A 14-day dose-response study of the efficacy, safety, and pharmacokinetics of the nonpeptidic protease inhibitor tipranavir in treatment-naive HIV-1-infected patients. J Acquir Immune Defic Syndr. 2004;4:376-382.
34. Yuen GJ, Weller S, Pakes GE. A review of the pharmacokinetics of abacavir. Clin Pharmacokinet. 2008;6:351-371.
35. Narang VS, Lulla A, Malhotra G, et al. Pharmacokinetic profiling and bioequivalence evaluation of 2 lamivudine tablet formulations after single oral administration in healthy human Indian volunteers. J Acquir Immune Defic Syndr. 2005;5:566-569.
36. Droste JA, Verweij-van Wissen CP, Kearney BP, et al. Pharmacokinetic study of tenofovir disoproxil fumarate combined with rifampin in healthy volunteers. Antimicrob Agents Chemother. 2005;2:680-684.
37. Marier JF, Manthos H, Kebir S, et al. Comparative bioavailability study of zidovudine administered as two different tablet formulations in healthy adult subjects. Int J Clin Pharmacol Ther. 2006;5:240-246.
38. Liu P, Foster G, LaBadie RR, et al. Pharmacokinetic interaction between voriconazole and efavirenz at steady state in healthy male subjects. J Clin Pharmacol. 2008;1:73-84.
39. Tarinas A, Tapanes RD, Gonzalez D, et al. Bioequivalence study of two nevirapine tablet formulations in human-immunodeficiency-virus-infected patients. Farm Hosp. 2007;3:165-168.
40. MacArthur RD, Novak RM. Reviews of anti-infective agents: maraviroc: the first of a new class of antiretroviral agents. Clin Infect Dis. 2008;2: 236-241.
41. Haan C, Behrmann I. A cost effective non-commercial ECL-solution for Western blot detections yielding strong signals and low background. J Immunol Methods. 2007;1-2:11-19.
42. Barrett JC, Fry B, Maller J, et al. Haploview: analysis and visualization of LD and haplotype maps. Bioinformatics. 2005;2:263-265.
43. Halperin E, Eskin E. Haplotype reconstruction from genotype data using Imperfect Phylogeny. Bioinformatics. 2004;12:1842-1849.
44. Leger P, Dillingham R, Beauharnais CA, et al. CYP2B6 variants and plasma efavirenz concentrations during antiretroviral therapy in Port-au-Prince, Haiti. J Infect Dis. 2009;6:955-964.
45. Haas DW, Gebretsadik T, Mayo G, et al. Associations between CYP2B6 polymorphisms and pharmacokinetics after a single dose of nevirapine or efavirenz in African americans. J Infect Dis. 2009;6:872-880.
46. Bosch TM, Deenen M, Pruntel R, et al. Screening for polymorphisms in the PXR gene in a Dutch population. Eur J Clin Pharmacol. 2006;5:395-399.
47. Lamba JK, Lin YS, Thummel K, et al. Common allelic variants of cytochrome P4503A4 and their prevalence in different populations. Pharmacogenetics. 2002;2:121-132.
48. Dai D, Tang J, Rose R, et al. Identification of variants of CYP3A4 and characterization of their abilities to metabolize testosterone and chlorpyrifos. J Pharmacol Exp Ther. 2001;3:825-831.
49. Matsumura K, Saito T, Takahashi Y, et al. Identification of a novel polymorphic enhancer of the human CYP3A4 gene. Mol Pharmacol. 2004;2:326-334.
50. Garsa AA, McLeod HL, Marsh S. CYP3A4 and CYP3A5 genotyping by pyrosequencing. BMC Med Genet. 2005;19.
51. Rodriguez-Antona C, Sayi JG, Gustafsson LL, et al. Phenotype-genotype variability in the human CYP3A locus as assessed by the probe drug quinine and analyses of variant CYP3A4 alleles. Biochem Biophys Res Commun. 2005;1:299-305.
52. Wyen C, Hendra H, Vogel M, et al. Impact of CYP2B6 983T.C polymorphism on non-nucleoside reverse transcriptase inhibitor plasma concentrations in HIV-infected patients. J Antimicrob Chemother. 2008;4: 914-918.
53. Kosoy R, Nassir R, Tian C, et al. Ancestry informative marker sets for determining continental origin and admixture proportions in common populations in America. Hum Mutat. 2009;1:69-78.
54. Stohr W, Back D, Dunn D, et al. Factors influencing efavirenz and nevirapine plasma concentration: effect of ethnicity, weight and co-medication. Antivir Ther. 2008;5:675-685.
55. Tedaldi EM, Absalon J, Thomas AJ, et al. Ethnicity, race, and gender. Differences in serious adverse events among participants in an antiretroviral initiation trial: results of CPCRA 058 (FIRST Study). J Acquir Immune Defic Syndr. 2008;4:441-448.
56. Watkins RE, Wisely GB, Moore LB, et al. The human nuclear xenobiotic receptor PXR: structural determinants of directed promiscuity. Science. 2001;5525:2329-2333.
57. Wang J, Sonnerborg A, Rane A, et al. Identification of a novel specific CYP2B6 allele in Africans causing impaired metabolism of the HIV drug efavirenz. Pharmacogenet Genomics. 2006;3:191-198.
58. Kawamoto T, Sueyoshi T, Zelko I, et al. Phenobarbital-responsive nuclear translocation of the receptor CAR in induction of the CYP2B gene. Mol Cell Biol. 1999;9:6318-6322.
59. Kozawa M, Honma M, Suzuki H. Quantitative prediction of in vivo profiles of CYP3A4 induction in humans from in vitro results with a reporter gene assay. Drug Metab Dispos. 2009;6:1234-1241.
60. Molto J, Blanco A, Miranda C, et al. Variability in non-nucleoside reverse transcriptase and protease inhibitors concentrations among HIV-infected adults in routine clinical practice. Br J Clin Pharmacol. 2007;6:715-721.
61. Murayama N, Nakamura T, Saeki M, et al. CYP3A4 gene polymorphisms influence testosterone 6beta-hydroxylation. Drug Metab Pharmacokinet. 2002;2:150-156.
62. Kang YS, Park SY, Yim CH, et al. The CYP3A4*18 genotype in the cytochrome P450 3A4 gene, a rapid metabolizer of sex steroids, is associated with low bone mineral density. Clin Pharmacol Ther. 2009;3: 312-318.
63. Eiselt R, Domanski TL, Zibat A, et al. Identification and functional characterization of eight CYP3A4 protein variants. Pharmacogenetics. 2001;5:447-458.
64. NCBI/The HapMap Project: Samples from Yoruba in Ibadan, Nigeria. Available at: http://www.ncbi.nlm.nih.gov/SNP/snp-viewTable.cgi?pop=1412. Accessed August 15, 2008.
65. GeneCards Human Gene Database. Available at: http://www.genecards.org/ cgi-bin/carddisp.pl?gene=CYP3A4&search=rs4987159&snp=322&snp-sort- mode=140#snp. Accessed November 17, 2009.
66. Rotger M, Tegude H, Colombo S, et al. Predictive value of known and novel alleles of CYP2B6 for efavirenz plasma concentrations in HIV-infected individuals. Clin Pharmacol Ther. 2007;4:557-566.
67. Rotger M, Colombo S, Furrer H, et al. Does tenofovir influence efavirenz pharmacokinetics? Antivir Ther. 2007;1:115-118.
68. Gatanaga H, Hayashida T, Tsuchiya K, et al. Successful efavirenz dose reduction in HIV type 1-infected individuals with cytochrome P450 2B6 *6 and *26. Clin Infect Dis. 2007;9:1230-1237.
69. Jinno H, Tanaka-Kagawa T, Ohno A, et al. Functional characterization of cytochrome P450 2B6 allelic variants. Drug Metab Dispos. 2003;4: 398-403.
70. Kirchheiner J, Klein C, Meineke I, et al. Bupropion and 4-OH-bupropion pharmacokinetics in relation to genetic polymorphisms in CYP2B6. Pharmacogenetics. 2003;10:619-626.
71. Motsinger AA, Ritchie MD, Shafer RW, et al. Multilocus genetic interactions and response to efavirenz-containing regimens: an adult AIDS clinical trials group study. Pharmacogenet Genomics. 2006;11: 837-845.
72. Bertrand J, Treluyer JM, Panhard X, et al. Influence of pharmacogenetics on indinavir disposition and short-term response in HIV patients initiating HAART. Eur J Clin Pharmacol. 2009;7:667-678.