Partial deletion of CYP2B6 owing to unequal crossover with CYP2B7

Pharmacogenetics and Genomics

Volumn 17, Issue 10, 2007, Pages 885-890

  Rotger, Margalida ^a   Saumoy, Maria ^a   Zhang, Kunlin ^a   Flepp, Markus ^b   Sahli, Roland ^a   Decosterd, Laurent ^a   Telenti, Amalio ^a   Battegay, M ^e   Bernasconi, E ^e   Boni J ^e   Bucher, H C ^e   Burgisser Ph ^e   Cattacin, S ^e   Cavassini, M ^e   Dubs, R ^e   Egger, M ^e   Elzi, L ^e   Erb, P ^e   Fischer, M ^e   Flepp, M ^e   Fontana, A ^e   Francioli, P ^a   Furrer, H ^c   Gorgievski, M ^e   Gunthard H ^e   Hirsch, H ^e   Hirschel, B ^e   Hosli I ^e   Kahlert, Ch ^e   Kaiser, L ^e   Karrer, U ^e   Kind, C ^e   Klimkait, Th ^e   Ledergerber, B ^e   Martinetti, G ^e   Martinez, B ^e   Muller N ^e   Nadal, D ^e   Opravil, M ^e   Paccaud, F ^e   Pantaleo, G ^e   Rickenbach, M ^d   Rudin, C ^e   Schmid, P ^e   Schultze, D ^e   Schupbach J ^e   Speck, R ^e   Taffe P ^e   Tarr, P ^e   Telenti, A ^e   Trkola, A ^e   Vernazza, P ^e   Weber, R ^e   Yerly, S ^e   more..

^a LAUSANNE UNIVERSITY HOSPITAL   (Switzerland)

^b Center for Vascular Diseases   (Switzerland)

^c Clinical and Laboratory Committee

^d Data Center

^e Clinical and Laboratory Committee ^*

Author keywords

Efavirenz; Gene deletion; Pharmacogenetics; Unequal crossover

Indexed keywords

ABACAVIR; ANTIRETROVIRUS AGENT; CYTOCHROME P450 2B; CYTOCHROME P450 2B6; CYTOCHROME P450 2B7; EFAVIRENZ; ISOENZYME; LOPINAVIR; TENOFOVIR; UNCLASSIFIED DRUG;

ALLELE; AMINO ACID SUBSTITUTION; AREA UNDER THE CURVE; ARTICLE; COMPUTER MODEL; CROSSING OVER; DNA POLYMORPHISM; DRUG BLOOD LEVEL; DRUG DOSE REDUCTION; ENZYME SUBSTRATE; EXON; GENE DELETION; GENE LOCUS; GENE MAPPING; GENE NUMBER; GENE SEQUENCE; GENETIC ANALYSIS; GENETIC IDENTIFICATION; GENETIC RECOMBINATION; GENETIC VARIABILITY; HETEROZYGOTE; HUMAN; HUMAN IMMUNODEFICIENCY VIRUS 1; HUMAN IMMUNODEFICIENCY VIRUS INFECTED PATIENT; HUMAN IMMUNODEFICIENCY VIRUS INFECTION; INTRON; MOLECULAR WEIGHT; NUCLEOTIDE SEQUENCE; PHENOTYPE; POLYMERASE CHAIN REACTION; PRIORITY JOURNAL; QUANTITATIVE ANALYSIS; SOUTHERN BLOTTING;

ARYL HYDROCARBON HYDROXYLASES; CHROMOSOME MAPPING; CROSSING OVER, GENETIC; CYTOCHROME P-450 ENZYME SYSTEM; EXONS; GENE DELETION; GENE DOSAGE; HUMANS; OXIDOREDUCTASES, N-DEMETHYLATING; RECOMBINATION, GENETIC;

HUMAN IMMUNODEFICIENCY VIRUS 1;

EID: 34648837873     PISSN: 17446872     EISSN: 17446880     Source Type: Journal    
DOI: 10.1097/FPC.0b013e3282ef5cd1     Document Type: Article

References (42)

1. Ekins S, Wrighton SA. The role of CYP2B6 in human xenobiotic metabolism. Drug Metab Rev 1999; 31:719-754.
2. Erickson DA, Mather G, Trager WF, Levy RH, Keirns JJ. Characterization of the in vitro biotransformation of the HIV-1 reverse transcriptase inhibitor nevirapine by human hepatic cytochromes P-450. Drug Metab Dispos 1999; 27:1488-1495.
3. Ward BA, Gorski JC, Jones DR, Hall SD, Flockhart DA, Desta Z. The cytochrome P450 2B6 (CYP2B6) is the main catalyst of efavirenz primary and secondary metabolism: implication for HIV/AIDS therapy and utility of efavirenz as a substrate marker of CYP2B6 catalytic activity. J Pharmacol Exp Ther 2003; 306:287-300.
4. Riska P, Lamson M, MacGregor T, Sabo J, Hattox S, Pav J, et al. Disposition and biotransformation of the antiretroviral drug nevirapine in humans. Drug Metab Dispos 1999; 27:895-901.
5. Turpeinen M, Raunio H, Pelkonen O. The functional role of CYP2B6 in human drug metabolism: substrates and inhibitors in vitro, in vivo and in silico. Curr Drug Metab 2006; 7:705-714.
6. Loboz KK, Gross AS, Williams KM, Liauw WS, Day RO, Blievernicht JK, et al. Cytochrome P450 2B6 activity as measured by bupropion hydroxylation: effect of induction by rifampin and ethnicity. Clin Pharmacol Ther 2006; 80:75-84.
7. Richter T, Murdter TE, Heinkele G, Pleiss J, Tatzel S, Schwab M, et al. Potent mechanism-based inhibition of human CYP2B6 by clopidogrel and ticlopidine. J Pharmacol Exp Ther 2004; 308:189-197.
8. Richter T, Schwab M, Eichelbaum M, Zanger UM. Inhibition of human CYP2B6 by N,N′,N″-triethylenethiophosphoramide is irreversible and mechanism-based. Biochem Pharmacol 2005; 69:517-524.
9. Saussele T, Burk O, Blievernicht JK, Klein K, Nussler A, Nussler N, et al. Selective induction of human hepatic cytochromes P450 2B6 and 3A4 by metamizole. Clin Pharmacol Ther 2007.
10. Turpeinen M, Tolonen A, Uusitalo J, Jalonen J, Pelkonen O, Laine K. Effect of clopidogrel and ticlopidine on cytochrome P450 2B6 activity as measured by bupropion hydroxylation. Clin Pharmacol Ther 2005; 77:553-559.
11. Hoffman SM, Nelson DR, Keeney DS. Organization, structure and evolution of the CYP2 gene cluster on human chromosome 19. Pharmacogenetics 2001; 11:687-698.
12. Chang TK, Bandiera SM, Chen J. Constitutive androstane receptor and pregnane X receptor gene expression in human liver: interindividual variability and correlation with CYP2B6 mRNA levels. Drug Metab Dispos 2003; 31:7-10.
13. Honkakoski P, Zelko I, Sueyoshi T, Negishi M. The nuclear orphan receptor CAR-retinoid X receptor heterodimer activates the phenobarbital-responsive enhancer module of the CYP2B gene. Mol Cell Biol 1998; 18:5652-5658.
14. Lamba JK, Lamba V, Yasuda K, Lin YS, Assem M, Thompson E, et al. Expression of constitutive androstane receptor splice variants in human tissues and their functional consequences. J Pharmacol Exp Ther 2004; 311:811-821.
15. Haas DW, Ribaudo HJ, Kim RB, Tierney C, Wilkinson GR, Gulick RM, et al. Pharmacogenetics of efavirenz and central nervous system side effects: an Adult AIDS Clinical Trials Group study. AIDS 2004; 18:2391-2400.
16. Hesse LM, He P, Krishnaswamy S, Hao Q, Hogan K, von Moltke LL, et al. Pharmacogenetic determinants of interindividual variability in bupropion hydroxylation by cytochrome P450 2B6 in human liver microsomes. Pharmacogenetics 2004; 14:225-238.
17. Klein K, Lang T, Saussele T, Barbosa-Sicard E, Schunck WH, Eichelbaum M, et al. Genetic variability of CYP2B6 in populations of African and Asian origin: allele frequencies, novel functional variants, and possible implications for anti-HIV therapy with efavirenz. Pharmacogenet Genomics 2005; 15:861-873.
18. Lamba V, Lamba J, Yasuda K, Strom S, Davila J, Hancock ML, et al. Hepatic CYP2B6 expression: gender and ethnic differences and relationship to CYP2B6 genotype and CAR (constitutive androstane receptor) expression. J Pharmacol Exp Ther 2003; 307:906-922.
19. Lang T, Klein K, Fischer J, Nussler AK, Neuhaus P, Hofmann U, et al. Extensive genetic polymorphism in the human CYP2B6 gene with impact on expression and function in human liver. Pharmacogenetics 2001; 11:399-415.
20. Lang T, Klein K, Richter T, Zibat A, Kerb R, Eichelbaum M, et al. Multiple novel nonsynonymous CYP2B6 gene polymorphisms in Caucasians: demonstration of phenotypic null alleles. J Pharmacol Exp Ther 2004; 311:34-43.
21. Rotger M, Tegude H, Colombo S, Cavassini M, Furrer H, Decosterd L, et al. Predictive value of known and novel alleles of CYP2B6 for efavirenz plasma concentrations in HIV-infected individuals. Clin Pharmacol Ther 2007; 81:557-566.
22. Wang J, Sonnerborg A, Rane A, Josephson F, Lundgren S, Stahle L, et al. Identification of a novel specific CYP2B6 allele in Africans causing impaired metabolism of the HIV drug efavirenz. Pharmacogenet Genomics 2006; 16:191-198.
23. Zukunft J, Lang T, Richter T, Hirsch-Ernst KI, Nussler AK, Klein K, et al. A natural CYP2B6 TATA box polymorphism (-82T - > C) leading to enhanced transcription and relocation of the transcriptional start site. Mol Pharmacol 2005; 67:1772-1782.
24. Gaedigk A, Blum M, Gaedigk R, Eichelbaum M, Meyer UA. Deletion of the entire cytochrome P450 CYP2D6 gene as a cause of impaired drug metabolism in poor metabolizers of the debrisoquine/sparteine polymorphism. Am J Hum Genet 1991; 48:943-950.
25. Johansson I, Lundqvist E, Bertilsson L, Dahl ML, Sjoqvist F, Ingelman-Sundberg M. Inherited amplification of an active gene in the cytochrome P450 CYP2D locus as a cause of ultrarapid metabolism of debrisoquine. Proc Natl Acad Sci U S A 1993; 90:11825-11829.
26. Lamba JK, Chen X, Lan LB, Kim JW, Wei WX, Relling MV, et al. Increased CYP3A4 copy number in TONG/HCC cells but not in DNA from other humans. Pharmacogenet Genomics 2006; 16:415-427.
27. Nunoya K, Yokoi T, Takahashi Y, Kimura K, Kinoshita M, Kamataki T. Homologous unequal cross-over within the human CYP2A gene cluster as a mechanism for the deletion of the entire CYP2A6 gene associated with the poor metabolizer phenotype. J Biochem (Tokyo) 1999; 126:402-407.
28. Rao Y, Hoffmann E, Zia M, Bodin L, Zeman M, Sellers EM, et al. Duplications and defects in the CYP2A6 gene: identification, genotyping, and in vivo effects on smoking. Mol Pharmacol 2000; 58:747-755.
29. Csajka C, Marzolini C, Fattinger K, Decosterd LA, Fellay J, Telenti A, et al. Population pharmacokinetics and effects of efavirenz in patients with human immunodeficiency virus infection. Clin Pharmacol Ther 2003; 73:20-30.
30. Gonzalez E, Kulkarni H, Bolivar H, Mangano A, Sanchez R, Catano G, et al. The influence of CCL3L1 gene-containing segmental duplications on HIV-1/AIDS susceptibility. Science 2005; 307:1434-1440.
31. Jurka J. Repeats in genomic DNA: mining and meaning. Curr Opin Struct Biol 1998; 8:333-337.
32. Blievernicht JK, Schaeffeler E, Klein K, Eichelbaum M, Schwab M, Zanger UM. MALDI-TOF mass spectrometry for multiplex genotyping of CYP2B6 single-nucleotide polymorphisms. Clin Chem 2006; 53:24-33.
33. Eichler EE, Nickerson DA, Altshuler D, Bowcock AM, Brooks LD, Carter NP, et al. Human Genome Structural Variation Working Group. Completing the map of human genetic variation. Nature 2007; 447:161-165.
34. Iafrate AJ, Feuk L, Rivera MN, Listewnik ML, Donahoe PK, Qi Y, et al. Detection of large-scale variation in the human genome. Nat Genet 2004; 36:949-951.
35. McCarroll SA, Hadnott TN, Perry GH, Sabeti PC, Zody MC, Barrett JC, et al. Common deletion polymorphisms in the human genome. Nat Genet 2006; 38:86-92.
36. Sebat J, Lakshmi B, Troge J, Alexander J, Young J, Lundin P, et al. Large-scale copy number polymorphism in the human genome. Science 2004; 305:525-528.
37. Ouahchi K, Lindeman N, Lee C. Copy number variants and pharmacogenomics. Pharmacogenomics 2006; 7:25-29.
38. Panserat S, Mura C, Gerard N, Vincent-Viry M, Galteau MM, Jacoz-Aigrain E, et al. An unequal cross-over event within the CYP2D gene cluster generates a chimeric CYP2D7/CYP2D6 gene which is associated with the poor metabolizer phenotype. Br J Clin Pharmacol 1995; 40:361-367.
39. Steen VM, Molven A, Aarskog NK, Gulbrandsen AK. Homologous unequal cross-over involving a 2.8 kb direct repeat as a mechanism for the generation of allelic variants of human cytochrome P450 CYP2D6 gene. Hum Mol Genet 1995; 4:2251-2257.
40. Gaedigk A, Ndjountche L, Divakaran K, Dianne BL, Zineh I, Oberlander TF, et al. Cytochrome P4502D6 (CYP2D6) gene locus heterogeneity: characterization of gene duplication events. Clin Pharmacol Ther 2007; 81:242-251.
41. Oscarson M, McLellan RA, Asp V, Ledesma M, Bernal Ruiz ML, Sinues B, et al. Characterization of a novel CYP2A7/CYP2A6 hybrid allele (CYP2A6*12) that causes reduced CYP2A6 activity. Hum Mutat 2002; 20:275-283.
42. Batzer MA, Deininger PL. Alu repeats and human genomic diversity. Nat Rev Genet 2002; 3:370-379.