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Chapter 52 : Genetically Polymorphic Cytochrome P450s and Transporters and Personalized Antimicrobial Chemotherapy

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Abstract:

This chapter summarizes a number of functionally important genetic polymorphisms in drug-metabolizing enzymes and drug transporters and their genotyping methodologies, by which individuals susceptible to drug toxicity or loss of efficacy can be identified or predicted easily in the clinical setting. The human cytochrome P450 (CYP) enzyme system contributing to drug metabolism comprises the CYP families CYP1, CYP2, and CYP3. Among these CYPs, proteins encoded by the human CYP3A genes catalyze the metabolism of nearly half of all currently used drugs, and approximately 40% of all marketed drugs are substrates for CYP2C9, CYP2C19, and CYP2D6. Moreover, the CYP2B6, CYP2C9, CYP2C19, and CYP2D6 enzymes exhibit large variations in the levels of their protein expression and enzymatic activity as a result of frequently occurring, functionally important genetic polymorphisms. Typically, in addition to passive diffusion, a drug is transported into cells by uptake (or influx) transporters, such as organic anion transporters (OATs), organic anion transport peptides (OATPs), and organic cation transporters (OCTs), whereas the drug and its metabolite(s) are removed from the cells by efflux transporters, such as P-glycoprotein (P-gp), multidrug resistance proteins (MRPs), and breast cancer resistance protein (BCRP). Anti-infective drugs may be substrates for some uptake transporters, drug-metabolizing enzymes, and efflux transporters.

Citation: Xie H. 2011. Genetically Polymorphic Cytochrome P450s and Transporters and Personalized Antimicrobial Chemotherapy, p 803-832. In Persing D, Tenover F, Tang Y, Nolte F, Hayden R, van Belkum A (ed), Molecular Microbiology. ASM Press, Washington, DC. doi: 10.1128/9781555816834.ch52

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FIGURE 1

The four interrelationships between infectious pathogens, their hosts (i.e., patients), and anti-infective drugs.

Citation: Xie H. 2011. Genetically Polymorphic Cytochrome P450s and Transporters and Personalized Antimicrobial Chemotherapy, p 803-832. In Persing D, Tenover F, Tang Y, Nolte F, Hayden R, van Belkum A (ed), Molecular Microbiology. ASM Press, Washington, DC. doi: 10.1128/9781555816834.ch52
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Image of FIGURE 2
FIGURE 2

Genetic polymorphisms in the human gene and their localizations.

Citation: Xie H. 2011. Genetically Polymorphic Cytochrome P450s and Transporters and Personalized Antimicrobial Chemotherapy, p 803-832. In Persing D, Tenover F, Tang Y, Nolte F, Hayden R, van Belkum A (ed), Molecular Microbiology. ASM Press, Washington, DC. doi: 10.1128/9781555816834.ch52
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Image of FIGURE 3
FIGURE 3

Polymorphisms in the human gene and their localizations. For more updated information, see http://www.cypalleles.ki.se/cyp2c19.htm.

Citation: Xie H. 2011. Genetically Polymorphic Cytochrome P450s and Transporters and Personalized Antimicrobial Chemotherapy, p 803-832. In Persing D, Tenover F, Tang Y, Nolte F, Hayden R, van Belkum A (ed), Molecular Microbiology. ASM Press, Washington, DC. doi: 10.1128/9781555816834.ch52
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Image of FIGURE 4
FIGURE 4

Intracellular drug concentrations (available for drug action) are the result of interplay between drug transporters (uptake and efflux) and drug-metabolizing enzymes (DMEs) for a given drug. The main influx (or uptake) transporters include OATs, OATPs, and OCTs; efflux transporters include P-gp, MRPs, and BCRP; and DMEs include P450s and Phase II DMEs, such as uridine diphosphate glucuronyltransferase (UGT) and -acetyltransferase 2 (NAT2).

Citation: Xie H. 2011. Genetically Polymorphic Cytochrome P450s and Transporters and Personalized Antimicrobial Chemotherapy, p 803-832. In Persing D, Tenover F, Tang Y, Nolte F, Hayden R, van Belkum A (ed), Molecular Microbiology. ASM Press, Washington, DC. doi: 10.1128/9781555816834.ch52
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References

/content/book/10.1128/9781555816834.ch52
1. Aithal, G. P.,, C. P. Day,, J. B. Leathart, and, A. K. Daly. 2000. Relationship of polymorphism in CYP2C9 to genetic susceptibility to diclofenac-induced hepatitis. Pharmacogenetics 10:511518.
2. Alderborn, A.,, A. Kristofferson, and, U. Hammerling. 2000. Determination of single-nucleotide polymorphisms by real-time pyrophosphate DNA sequencing. Genome Res. 10:12491258.
3. Allabi, A. C.,, J. L. Gala, and, Y. Horsmans. 2005. CYP2C9, CYP2C19, ABCB1 (MDR1) genetic polymorphisms and phenytoin metabolism in a Black Beninese population. Pharmacogenet. Genomics 15:779786.
4. Ambudkar, S. V.,, S. Dey,, C. A. Hrycyna,, M. Ramachandra,, I. Pastan, and, M. M. Gottesman. 1999. Biochemical, cellular, and pharmacological aspects of the multidrug transporter. Annu. Rev. Pharmacol. Toxicol. 39:361398.
5. Ameyaw, M. M.,, F. Regateiro,, T. Li,, X. Liu,, M. Tariq,, A. Mobarek,, N. Thornton,, G. O. Folayan,, J. Githang’a,, A. Indalo,, D. Ofori-Adjei,, D. A. Price-Evans, and, H. L. McLeod. 2001. MDR1 pharmacogenetics: frequency of the C3435T mutation in exon 26 is significantly influenced by ethnicity. Pharmacogenetics 11:217221.
6. Anderson, P. L.,, J. Lamba,, C. L. Aquilante,, E. Schuetz, and, C. V. Fletcher. 2006. Pharmacogenetic characteristics of indinavir, zidovudine, and lamivudine therapy in HIV-infected adults: a pilot study. J. Acquir. Immune Defic. Syndr. 42:441449.
7. Anonymous. 2005. AmpliChip CYP450 test. Med. Lett. Drugs Ther. 47:7172.
8. Aoyama, T.,, S. Yamano,, D. J. Waxman,, D. P. Lapenson,, U. A. Meyer,, V. Fischer,, R. Tyndale,, T. Inaba,, W. Kalow, and, H. V. Gelboin. 1989. Cytochrome P-450 hPCN3, a novel cytochrome P-450 IIIA gene product that is differentially expressed in adult human liver. cDNA and deduced amino acid sequence and distinct specificities of cDNA-expressed hPCN1 and hPCN3 for the metabolism of steroid hormones and cyclosporine. J. Biol. Chem. 264:1038810395.
9. Aplenc, R.,, W. Glatfelter,, P. Han,, E. Rappaport,, M. La,, A. Cnaan,, M. A. Blackwood,, B. Lange, and, T. Rebbeck. 2003. CYP3A genotypes and treatment response in paediatric acute lymphoblastic leukaemia. Br. J. Haematol. 122:240244.
10. Ariyoshi, N.,, M. Miyazaki,, K. Toide,, Y. Sawamura, and, T. Kamataki. 2001. A single nucleotide polymorphism of CYP2B6 found in Japanese enhances catalytic activity by autoactivation. Biochem. Biophys. Res. Commun. 281:12561260.
11. Aynacioglu, A. S.,, J. Brockmöller,, S. Bauer,, C. Sachse,, P. Güzelbey,, Z. Ongen,, M. Nacak, and, I. Roots. 1999. Frequency of cytochrome P450 CYP2C9 variants in a Turkish population and functional relevance for phenytoin. Br. J. Clin. Pharmacol. 48:409415.
12. Baede-van Dijk, P. A.,, P. W. Hugen,, C. P. Verweij-van Wissen,, P. P. Koopmans,, D. M. Burger, and, Y. A. Hekster. 2001. Analysis of variation in plasma concentrations of nelfinavir and its active metabolite M8 in HIV-positive patients. AIDS 15:991998.
13. Bai, S. L.,, X. Zhong,, L. Ma,, W. Zheng,, L. M. Fan,, N. Wei, and, X. W. Deng. 2007. A simple and reliable assay for detecting specific nucleotide sequences in plants using optical thin-film biosensor chips. Plant J. 49:354366.
14. Balram, C.,, Q. Zhou,, Y. B. Cheung, and, E. J. Lee. 2003. CYP3A5*3 and *6 single nucleotide polymorphisms in three distinct Asian populations. Eur. J. Clin. Pharmacol. 59:123126.
15. Bathum, L.,, T. S. Hansen,, M. Horder, and, K. Brøsen. 1998. A dual label oligonucleotide ligation assay for detection of the CYP2C19*1, CYP2C19*2, and CYP2C19*3 alleles involving time-resolved fluorometry. Ther. Drug Monit. 20:16.
16. Blaisdell, J.,, L. F. Jorge-Nebert,, S. Coulter,, S. S. Ferguson,, S. J. Lee,, B. Chanas,, T. Xi,, H. Mohrenweiser,, B. Ghanayem, and, J. A. Goldstein. 2004. Discovery of new potentially defective alleles of human CYP2C9. Pharmacogenetics 14:527537.
17. Blaisdell, J.,, H. Mohrenweiser,, J. Jackson,, S. Ferguson,, S. Coulter,, B. Chanas,, T. Xi,, B. Ghanayem, and, J. A. Goldstein. 2002. Identification and functional characterization of new potentially defective alleles of human CYP2C19. Pharmacogenetics 12:703711.
18. Bleasby, K.,, L. A. Hall,, J. L. Perry,, H. W. Mohrenweiser, and, J. B. Pritchard. 2005. Functional consequences of single nucleotide polymorphisms in the human organic anion transporter hOAT1 (SLC22A6). J. Pharmacol. Exp. Ther. 314:923931.
19. Blievernicht, J. K.,, E. Schaeffeler,, K. Klein,, M. Eichelbaum,, M. Schwab, and, U. M. Zanger. 2007. MALDI-TOF mass spectrometry for multiplex genotyping of CYP2B6 single-nucleotide polymorphisms. Clin. Chem. 53:2433.
20. Brandt, J. T.,, S. L. Close,, S. J. Iturria,, C. D. Payne,, N. A. Farid,, C. S. Ernest,, D. R. Lachno,, D. Salazar, and, K. J. Winters. 2007. Common polymorphisms of CYP2C19 and CYP2C9 affect the pharmacokinetic and pharmacodynamic response to clopidogrel but not prasugrel. J. Thromb. Haemost. 5:24292436.
21. Brooks, B. A.,, O. W. McBride,, C. T. Dolphin,, M. Farrall,, P. J. Scambler,, F. J. Gonzalez, and, J. R. Idle. 1988. The gene CYP3 encoding P450pcn1 (nifedipine oxidase) is tightly linked to the gene COL1A2 encoding collagen type 1 alpha on 7q21-q22.1. Am. J. Hum. Genet. 43:280284.
22. Burger, D. M.,, H. R. Schwietert,, E. P. Colbers, and, M. Becker. 2006. The effect of the CYP2C19*2 heterozygote genotype on the pharmacokinetics of nelfinavir. Br. J. Clin. Pharmacol. 62:250252.
23. Cascorbi, I.,, T. Gerloff,, A. Johne,, C. Meisel,, S. Hoffmeyer,, M. Schwab,, E. Schaeffeler,, M. Eichelbaum,, U. Brinkmann, and, I. Roots. 2001. Frequency of single nucleotide polymorphisms in the P-glycoprotein drug transporter MDR1 gene in white subjects. Clin. Pharmacol. Ther. 69:169174.
24. Chantarangsu, S.,, T. Cressey,, S. Mahasirimongkol,, Y. Tawon,, N. Ngo-Giang-Huong,, G. Jourdain,, M. Lallemant, and, W. Chantratita. 2007. Comparison of the TaqMan and LightCycler systems in evaluation of CYP2B6 516G>T polymorphism. Mol. Cell. Probes 21:408411.
25. Chou, F. C.,, S. J. Tzeng, and, J. D. Huang. 2001. Genetic polymorphism of cytochrome P450 3A5 in Chinese. Drug Metab. Dispos. 29:12051209.
26. Coller, J. K.,, D. T. Barratt,, K. Dahlen,, M. H. Loennechen, and, A. A. Somogyi. 2006. ABCB1 genetic variability and methadone dosage requirements in opioiddependent individuals. Clin. Pharmacol. Ther. 80:682690.
27. Coller, J. K.,, A. A. Somogyi, and, F. Bochner. 1997. Association between CYP2C19 genotype and proguanil oxidative polymorphism. Br. J. Clin. Pharmacol. 43:659660.
28. Crettol, S.,, J. J. Déglon,, J. Besson,, M. Croquette-Krokkar,, I. Gothuey,, R. Hämmig,, M. Monnat,, H. Hüttemann,, P. Baumann, and, C. B. Eap. 2005. Methadone enantiomer plasma levels, CYP2B6, CYP2C19, and CYP2C9 genotypes, and response to treatment. Clin. Pharmacol. Ther. 78:593604.
29. Dai, D.,, J. Tang,, R. Rose,, E. Hodgson,, R. J. Bienstock,, H. W. Mohrenweiser, and, J. A. Goldstein. 2001. Identification of variants of CYP3A4 and characterization of their abilities to metabolize testosterone and chlorpyrifos. J. Pharmacol. Exp. Ther. 299:825831.
30. Dally, H.,, L. Edler,, B. Jäger,, P. Schmezer,, B. Spiegelhalder,, H. Dienemann,, P. Drings,, V. Schulz,, K. Kayser,, H. Bartsch, and, A. Risch. 2003. The CYP3A4*1B allele increases risk for small cell lung cancer: effect of gender and smoking dose. Pharmacogenetics 13:607618.
31. Davison, D. B.,, and J. F. Barrett. 2003. Antibiotics and pharmacogenomics. Pharmacogenomics 4:657665.
32. Deeley, R. G.,, and S. P. Cole. 2006. Substrate recognition and transport by multidrug resistance protein 1 (ABCC1). FEBS Lett. 580:11031111.
33. de Leon, J.,, M. T. Susce, and, E. Murray-Carmichael. 2006. The AmpliChip CYP450 genotyping test: integrating a new clinical tool. Mol. Diagn. Ther. 10:135151.
34. DeLozier, T. C.,, S. C. Lee,, S. J. Coulter,, B. C. Goh, and, J. A. Goldstein. 2005. Functional characterization of novel allelic variants of CYP2C9 recently discovered in Southeast Asians. J. Pharmacol. Exp. Ther. 315:10851090.
35. de Morais, S. M.,, J. A. Goldstein,, H. G. Xie,, S. L. Huang,, Y. Q. Lu,, H. Xia,, Z. S. Xiao,, N. Ile, and, H. H. Zhou. 1995. Genetic analysis of the S-mephenytoin polymorphism in a Chinese population. Clin. Pharmacol. Ther. 58:404411.
36. de Morais, S. M.,, G. R. Wilkinson,, J. Blaisdell,, U. A. Meyer,, K. Nakamura, and, J. A. Goldstein. 1994. Identification of a new genetic defect responsible for the polymorphism of (S)-mephenytoin metabolism in Japanese. Mol. Pharmacol. 46:594598.
37. de Morais, S. M.,, G. R. Wilkinson,, J. Blaisdell,, K. Nakamura,, U. A. Meyer, and, J. A. Goldstein. 1994. The major genetic defect responsible for the polymorphism of S-mephenytoin metabolism in humans. J. Biol. Chem. 269:1541915422.
38. Desta, Z.,, T. Saussele,, B. Ward,, J. Blievernicht,, L. Li,, K. Klein,, D. A. Flockhart, and, U. M. Zanger. 2007. Impact of CYP2B6 polymorphism on hepatic efavirenz metabolism in vitro. Pharmacogenomics 8:547558.
39. Dickmann, L. J.,, A. E. Rettie,, M. B. Kneller,, R. B. Kim,, A. J. Wood,, C. M. Stein,, G. R. Wilkinson, and, U. I. Schwarz. 2001. Identification and functional characterization of a new CYP2C9 variant (CYP2C9*5) expressed among African Americans. Mol. Pharmacol. 60:382387.
40. Domanski, T. L.,, C. Finta,, J. R. Halpert, and, P. G. Zaphiropoulos. 2001. cDNA cloning and initial characterization of CYP3A43, a novel human cytochrome P450. Mol. Pharmacol. 59:386392.
41. Eiselt, R.,, T. L. Domanski,, A. Zibat,, R. Mueller,, E. Presecan-Siedel,, E. Hustert,, U. M. Zanger,, J. Brockmoller,, H. P. Klenk,, U. A. Meyer,, K. K. Khan,, Y. A. He,, J. R. Halpert, and, L. Wojnowski. 2001. Identification and functional characterization of eight CYP3A4 protein variants. Pharmacogenetics 11:447458.
42. Erdman, A. R.,, L. M. Mangravite,, T. J. Urban,, L. L. Lagpacan,, R. A. Castro,, M. de la Cruz,, W. Chan,, C. C. Huang,, S. J. Johns,, M. Kawamoto,, D. Stryke,, T. R. Taylor,, E. J. Carlson,, T. E. Ferrin,, C. M. Brett,, E. G. Burchard, and, K. M. Giacomini. 2006. The human organic anion transporter 3 (OAT3; SLC22A8): genetic variation and functional genomics. Am. J. Physiol. Renal Physiol. 290:F905F912.
43. Evans, W. E.,, and M. V. Relling. 1999. Pharmacogenomics: translating functional genomics into rational therapeutics. Science 286:487491.
44. Fellay, J.,, C. Marzolini,, E. R. Meaden,, D. J. Back,, T. Buclin,, J. P. Chave,, L. A. Decosterd,, H. Furrer,, M. Opravil,, G. Pantaleo,, D. Retelska,, L. Ruiz,, A. H. Schinkel,, P. Vernazza,, C. B. Eap, and, A. Telenti. 2002. Response to antiretroviral treatment in HIV-1-infected individuals with allelic variants of the multidrug resistance transporter 1: a pharmacogenetics study. Lancet 359:3036.
45. Ferguson, R. J.,, S. M. de Morais,, S. Benhamou,, C. Bouchardy,, J. Blaisdell,, G. Ibeanu,, G. R. Wilkinson,, T. C. Sarich,, J. M. Wright,, P. Dayer, and, J. A. Goldstein. 1998. A new genetic defect in human CYP2C19: mutation of the initiation codon is responsible for poor metabolism of S-mephenytoin. J. Pharmacol. Exp. Ther. 284:356361.
46. Finta, C.,, and P. G. Zaphiropoulos. 2000. The human cytochrome P450 3A locus. Gene evolution by capture of downstream exons. Gene 260:1323.
47. Finta, C.,, and P. G. Zaphiropoulos. 2002. Intergenic mRNA molecules resulting from trans-splicing. J. Biol. Chem. 277:58825890.
48. Floyd, M. D.,, G. Gervasini,, A. L. Masica,, G. Mayo,, A. L. George, Jr.,, K. Bhat,, R. B. Kim, and, G. R. Wilkinson. 2003. Genotype-phenotype associations for common CYP3A4 and CYP3A5 variants in the basal and induced metabolism of midazolam in European- and African-American men and women. Pharmacogenetics 13:595606.
49. Fröhlich, M.,, M. M. Hoffmann,, J. Burhenne,, G. Mikus,, J. Weiss, and, W. E. Haefeli. 2004. Association of the CYP3A5 A6986G (CYP3A5*3) polymorphism with saquinavir pharmacokinetics. Br. J. Clin. Pharmacol. 58:443444.
50. Fujita, T.,, C. Brown,, E. J. Carlson,, T. Taylor,, M. de la Cruz,, S. J. Johns,, D. Stryke,, M. Kawamoto,, K. Fujita,, R. Castro,, C. W. Chen,, E. T. Lin,, C. M. Brett,, E. G. Burchard,, T. E. Ferrin,, C. C. Huang,, M. K. Leabman, and, K. M. Giacomini. 2005. Functional analysis of polymorphisms in the organic anion transporter, SLC22A6 (OAT1). Pharmacogenet. Genomics 15:201209.
51. Fukuen, S.,, T. Fukuda,, H. Maune,, Y. Ikenaga,, I. Yamamoto,, T. Inaba, and, J. Azuma. 2002. Novel detection assay by PCR-RFLP and frequency of the CYP3A5 SNPs, CYP3A5*3 and *6, in a Japanese population. Pharmacogenetics 12:331334.
52. Fukushima-Uesaka, H.,, Y. Saito,, K. Maekawa,, S. Ozawa,, R. Hasegawa,, H. Kajio,, N. Kuzuya,, K. Yasuda,, M. Kawamoto,, N. Kamatani,, K. Suzuki,, T. Yanagawa,, M. Tohkin, and, J. Sawada. 2005. Genetic variations and haplotypes of CYP2C19 in a Japanese population. Drug Metab. Pharmacokinet. 20:300307.
53. Furuya, H.,, P. Fernandez-Salguero,, W. Gregory,, H. Taber,, A. Steward,, F. J. Gonzalez, and, J. R. Idle. 1995. Genetic polymorphism of CYP2C9 and its effect on warfarin maintenance dose requirement in patients undergoing anticoagulation therapy. Pharmacogenetics 5:389392.
54. Futatsugawa, Y.,, T. Kubota,, A. Ishiguro,, H. Suzuki,, H. Ishikawa, and, T. Iga. 2004. PCR-based haplotype determination to distinguish CYP2B6*1/*7 and *5/*6. Clin. Chem. 50:14721473.
55. Gaedigk, A.,, W. L. Casley,, R. F. Tyndale,, E. M. Sellers,, M. Jurima-Romet, and, J. S. Leeder. 2001. Cytochrome P4502C9 (CYP2C9) allele frequencies in Canadian Native Indian and Inuit populations. Can. J. Physiol. Pharmacol. 79:841847.
56. Gaedigk, A.,, R. R. Gotschall,, N. S. Forbes,, S. D. Simon,, G. L. Kearns, and, J. S. Leeder. 1999. Optimization of cytochrome P4502D6 (CYP2D6) phenotype assignment using a genotyping algorithm based on allele frequency data. Pharmacogenetics 9:669682.
57. Gaedigk, A.,, S. D. Simon,, R. E. Pearce,, L. D. Bradford,, M. J. Kennedy, and, J. S. Leeder. 2008. The CYP2D6 activity score: translating genotype information into a qualitative measure of phenotype. Clin. Pharmacol. Ther. 83:234242.
58. Garsa, A. A.,, H. L. McLeod, and, S. Marsh. 2005. CYP3A4 and CYP3A5 genotyping by Pyrosequencing. BMC Med. Genet. 6:19.
59. Gatanaga, H.,, T. Hayashida,, K. Tsuchiya,, M. Yoshino,, T. Kuwahara,, H. Tsukada,, K. Fujimoto,, I. Sato,, M. Ueda,, M. Horiba,, M. Hamaguchi,, M. Yamamoto,, N. Takata,, A. Kimura,, T. Koike,, F. Gejyo,, S. Matsushita,, T. Shirasaka,, S. Kimura, and, S. Oka. 2007. Successful efavirenz dose reduction in HIV type 1-infected individuals with cytochrome P450 2B6 *6 and *26. Clin. Infect. Dis. 45:12301237.
60. Gellner, K.,, R. Eiselt,, E. Hustert,, H. Arnold,, I. Koch,, M. Haberl,, C. J. Deglmann,, O. Burk,, D. Buntefuss,, S. Escher,, C. Bishop,, H. G. Koebe,, U. Brinkmann,, H. P. Klenk,, K. Kleine,, U. A. Meyer, and, L. Wojnowski. 2001. Genomic organization of the human CYP3A locus: identification of a new, inducible CYP3A gene. Pharmacogenetics 11:111121.
61. Goldstein, J. A.,, and J. Blaisdell. 1996. Genetic tests which identify the principal defects in CYP2C19 responsible for the polymorphism in mephenytoin metabolism. Methods Enzymol. 272:210218.
62. Goldstein, J. A.,, and S. M. de Morais. 1994. Biochemistry and molecular biology of the human CYP2C subfamily. Pharmacogenetics 4:285299.
63. Gradhand, U.,, and R. B. Kim. 2008. Pharmacogenomics of MRP transporters (ABCC1-5) and BCRP (ABCG2). Drug Metab. Rev. 40:317354.
64. Griese, E. U.,, F. Lapple, and, M. Eichelbaum. 1999. Detection of CYP2C19 alleles *1, *2 and *3 by multiplex polymerase chain reaction. Pharmacogenetics 9:389391.
65. Guengerich, F. P. 1999. Cytochrome P-450 3A4: regulation and role in drug metabolism. Annu. Rev. Pharmacol. Toxicol. 39:117.
66. Guo, Y.,, Y. Wang,, D. Si,, P. J. Fawcett,, D. Zhong, and, H. Zhou. 2005. Catalytic activities of human cytochrome P450 2C9*1, 2C9*3 and 2C9*13. Xenobiotica 35:853861.
67. Guo, Y.,, Y. Zhang,, Y. Wang,, X. Chen,, D. Si,, D. Zhong,, J. P. Fawcett, and, H. Zhou. 2005. Role of CYP2C9 and its variants (CYP2C9*3 and CYP2C9*13) in the metabolism of lornoxicam in humans. Drug Metab. Dispos. 33:749753.
68. Gupta, S. K.,, S. L. Rosenkranz,, Y. S. Cramer,, S. L. Koletar,, L. A. Szczech,, V. Amorosa, and, S. D. Hall. 2008. The pharmacokinetics and pharmacogenomics of efavirenz and lopinavir/ritonavir in HIV-infected persons requiring hemodialysis. AIDS 22:19191927.
69. Haas, D. W. 2004. Pharmacogenomics of antiretroviral therapy. Drug Dev. Res. 62:213220.
70. Haas, D. W. 2005. Will pharmacogenomic discoveries improve HIV therapeutics? Top. HIV Med. 13:9095.
71. Haas, D. W.,, H. J. Ribaudo,, R. B. Kim,, C. Tierney,, G. R. Wilkinson,, R. M. Gulick,, D. B. Clifford,, T. Hulgan,, C. Marzolini, and, E. P. Acosta. 2004. Pharmacogenetics of efavirenz and central nervous system side effects: an Adult AIDS Clinical Trials Group study. AIDS 18:23912400.
72. Haas, D. W.,, L. M. Smeaton,, R. W. Shafer,, G. K. Robbins,, G. D. Morse,, L. Labbé,, G. R. Wilkinson,, D. B. Clifford,, R. T. D’Aquila,, V. De Gruttola,, R. B. Pollard,, T. C. Merigan,, M. S. Hirsch,, A. L. George, Jr.,, J. P. Donahue, and, R. B. Kim. 2005. Pharmacogenetics of long-term responses to antiretroviral regimens containing efavirenz and/or nelfinavir: an Adult Aids Clinical Trials Group Study. J. Infect. Dis. 192:19311942.
73. Hashimoto, H.,, K. Toide,, R. Kitamura,, M. Fujita,, S. Tagawa,, S. Itoh, and, T. Kamataki. 1993. Gene structure of CYP3A4, an adult-specific form of cytochrome P450 in human livers, and its transcriptional control. Eur. J. Biochem. 218:585595.
74. Hasse, B.,, H. F. Gunthard,, G. Bleiber, and, M. Krause. 2005. Efavirenz intoxication due to slow hepatic metabolism. Clin. Infect. Dis. 40:e22e23.
75. Heller, T.,, J. Kirchheiner,, V. W. Armstrong,, H. Luthe,, M. Tzvetkov,, J. Brockmöller, and, M. Oellerich. 2006. AmpliChip CYP450 GeneChip®: a new gene chip that allows rapid and accurate CYP2D6 genotyping. Ther. Drug Monit. 28:673677.
76. Herman, D.,, P. Peternel,, M. Stegnar,, K. Breskvar, and, V. Dolzan. 2006. A novel sequence variant in exon 7 of CYP2C9 gene (CYP2C9*24) in a patient on warfarin therapy. Thromb. Haemost. 95:192194.
77. Herrlin, K.,, A. Y. Massele,, M. Jande,, C. Alm,, G. Tybring,, Y. A. Abdi,, A. Wennerholm,, I. Johansson,, M. L. Dahl,, L. Bertilsson, and, L. L. Gustafsson. 1998. Bantu Tanzanians have a decreased capacity to metabolize omeprazole and mephenytoin in relation to their CYP2C19 genotype. Clin. Pharmacol. Ther. 64:391401.
78. Hersberger, M.,, J. Marti-Jaun,, K. Rentsch, and, E. Hanseler. 2001. Two single-tube tetra-primer assays to detect the CYP2C19*2 and *3 alleles of S-mephenytoin hydroxylase. Clin. Chem. 47:772774.
79. Hesse, L. M.,, P. He,, S. Krishnaswamy,, Q. Hao,, K. Hogan,, L. L. von Moltke,, D. J. Greenblatt, and, M. H. Court. 2004. Pharmacogenetic determinants of interindividual variability in bupropion hydroxylation by cytochrome P450 2B6 in human liver microsomes. Pharmacogenetics 14:225238.
80. Hesselink, D. A.,, R. H. van Schaik,, I. P. van der Heiden,, M. van der Werf,, P. J. Gregoor,, J. Lindemans,, W. Weimar, and, T. van Gelder. 2003. Genetic polymorphisms of the CYP3A4, CYP3A5, and MDR-1 genes and pharmacokinetics of the calcineurin inhibitors cyclosporine and tacrolimus. Clin. Pharmacol. Ther. 74:245254.
81. Hiratsuka, M.,, Y. Agatsuma, and, M. Mizugaki. 1999. Rapid detection of CYP2C9*3 alleles by real-time fluorescence PCR based on SYBR Green. Mol. Genet. Metab. 68:357362.
82. Hiratsuka, M.,, Y. Agatsuma,, F. Omori,, K. Narahara,, T. Inoue,, Y. Kishikawa, and, M. Mizugaki. 2000. High throughput detection of drug-metabolizing enzyme polymorphisms by allele-specific fluorogenic 5′ nuclease chain reaction assay. Biol. Pharm. Bull. 23:11311135.
83. Hiratsuka, M.,, Y. Takekuma,, N. Endo,, K. Narahara,, S. I. Hamdy,, Y. Kishikawa,, M. Matsuura,, Y. Agatsuma,, T. Inoue, and, M. Mizugaki. 2002. Allele and genotype frequencies of CYP2B6 and CYP3A5 in the Japanese population. Eur. J. Clin. Pharmacol. 58:417421.
84. Hirt, D.,, F. Mentré,, A. Tran,, E. Rey,, S. Auleley,, D. Salmon,, X. Duval,, J. M. Tréluyer, and the COPHARANRS Study Group. 2008. Effect of CYP2C19 polymorphism on nelfinavir to M8 biotransformation in HIV patients. Br. J. Clin. Pharmacol. 65:548557.
85. Hitzl, M.,, S. Drescher,, H. van der Kuip,, E. Schäffeler,, J. Fischer,, M. Schwab,, M. Eichelbaum, and, M. F. Fromm. 2001. 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 11:293298.
86. Hoffmeyer, S.,, O. Burk,, O. von Richter,, H. P. Arnold,, J. Brockmöller,, A. Johne,, I. Cascorbi,, T. Gerloff,, I. Roots,, M. Eichelbaum, and, U. Brinkmann. 2000. 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. USA 97:34733478.
87. Hsieh, K. P.,, Y. Y. Lin,, C. L. Cheng,, M. L. Lai,, M. S. Lin,, J. P. Siest, and, J. D. Huang. 2001. Novel mutations of CYP3A4 in Chinese. Drug Metab. Dispos. 29:268273.
88. Hulgan, T.,, and D. W. Haas. 2006. Toward a pharmacogenetic understanding of nucleotide and nucleoside analogue toxicity. J. Infect. Dis. 194:14711474.
89. Hustert, E.,, M. Haberl,, O. Burk,, R. Wolbold,, Y. Q. He,, K. Klein,, A. C. Nuessler,, P. Neuhaus,, J. Klattig,, R. Eiselt,, I. Koch,, A. Zibat,, J. Brockmöller,, J. R. Halpert,, U. M. Zanger, and, L. Wojnowski. 2001. The genetic determinants of the CYP3A5 polymorphism. Pharmacogenetics 11:773779.
90. Hyland, R.,, B. C. Jones, and, D. A. Smith. 2003. Identification of the cytochrome P450 enzymes involved in the N-oxidation of voriconazole. Drug Metab. Dispos. 31:540547.
91. Iannone, M. A.,, J. D. Taylor,, J. Chen,, M. S. Li,, P. Rivers,, K. A. Slentz-Kesler, and, M. P. Weiner. 2000. Multiplexed single nucleotide polymorphism genotyping by oligonucleotide ligation and flow cytometry. Cytometry 39:131140.
92. Ibeanu, G. C.,, J. Blaisdell,, R. J. Ferguson,, B. I. Ghanayem,, K. Brøsen,, S. Benhamou,, C. Bouchardy,, G. R. Wilkinson,, P. Dayer, and, J. A. Goldstein. 1999. A novel transversion in the intron 5 donor splice junction of CYP2C19 and a sequence polymorphism in exon 3 contribute to the poor metabolizer phenotype for the anticonvulsant drug S-mephenytoin. J. Pharmacol. Exp. Ther. 290:635640.
93. Ibeanu, G. C.,, J. Blaisdell,, B. I. Ghanayem,, C. Beyeler,, S. Benhamou,, C. Bouchardy,, G. R. Wilkinson,, P. Dayer,, A. K. Daly, and, J. A. Goldstein. 1998. An additional defective allele, CYP2C19*5, contributes to the S-mephenytoin poor metabolizer phenotype in Caucasians. Pharmacogenetics 8:129135.
94. Ibeanu, G. C.,, J. A. Goldstein,, U. Meyer,, S. Benhamou,, C. Bouchardy,, P. Dayer,, B. I. Ghanayem, and, J. Blaisdell. 1998. Identification of new human CYP2C19 alleles (CYP2C19*6 and CYP2C19*2B) in a Caucasian poor metabolizer of mephenytoin. J. Pharmacol. Exp. Ther. 286:14901495.
95. Idle, J. R.,, J. Corchero, and, F. J. Gonzalez. 2000. Medical implications of HGP’s sequence of chromosome 22. Lancet 355:319.
96. Ieiri, I.,, H. Tainaka,, T. Morita,, A. Hadama,, K. Mamiya,, M. Hayashibara,, H. Ninomiya,, S. Ohmori,, M. Kitada,, N. Tashiro,, S. Higuchi, and, K. Otsubo. 2000. Catalytic activity of three variants (Ile, Leu, and Thr) at amino acid residue 359 in human CYP2C9 gene and simultaneous detection using single-strand conformation polymorphism analysis. Ther. Drug Monit. 22:237244.
97. Imai, J.,, I. Ieiri,, K. Mamiya,, S. Miyahara,, H. Furuumi,, E. Nanba,, M. Yamane,, Y. Fukumaki,, H. Ninomiya,, N. Tashiro,, K. Otsubo, and, S. Higuchi. 2000. Polymorphism of the cytochrome P450 (CYP) 2C9 gene in Japanese epileptic patients: genetic analysis of the CYP2C9 locus. Pharmacogenetics 10:8589.
98. Inoue, K.,, J. Inazawa,, H. Nakagawa,, T. Shimada,, H. Yamazaki,, F. P. Guengerich, and, T. Abe. 1992. Assignment of the human cytochrome P-450 nifedipine oxidase gene (CYP3A4) to chromosome 7 at band q22.1 by fluorescence in situ hybridization. Jpn. J. Hum. Genet. 37:133138.
99. Inoue, K.,, H. Yamazaki,, K. Imiya,, S. Akasaka,, F. P. Guengerich, and, T. Shimada. 1997. Relationship between CYP2C9 and 2C19 genotypes and tolbutamide methyl hydroxylation and S-mephenytoin 4′-hydroxylation activities in livers of Japanese and Caucasian populations. Pharmacogenetics 7:103113.
100. Ito, S.,, I. Ieiri,, M. Tanabe,, A. Suzuki,, S. Higuchi, and, K. Otsubo. 2001. Polymorphism of the ABC transporter genes, MDR1, MRP1 and MRP2/cMOAT, in healthy Japanese subjects. Pharmacogenetics 11:175184.
101. Itoh, K.,, K. Inoue,, H. Nakao,, S. Yanagiwara,, H. Tada, and, T. Suzuki. 2000. Polymerase chain reaction-single-strand conformation polymorphism based determination of two major genetic defects responsible for a phenotypic polymorphism of cytochrome P450 (CYP) 2C19 in the Japanese population. Anal. Biochem. 284:160162.
102. Itoh, K.,, K. Inoue,, S. Yanagiwara,, H. Kyoya, and, T. Suzuki. 1999. A rapid and simple detection of genetic defects responsible for the phenotypic polymorphism of cytochrome P450 2C19. Biol. Pharm. Bull. 22:7779.
103. Izzedine, H.,, J. S. Hulot,, E. Villard,, C. Goyenvalle,, S. Dominguez,, J. Ghosn,, M. A. Valantin,, P. Lechat, and, A. G. Deray. 2006. Association between ABCC2 gene haplotypes and tenofovir-induced proximal tubulopathy. J. Infect. Dis. 194:14811491.
104. Jacob, R. M.,, E. C. Johnstone,, M. J. Neville, and, R. T. Walton. 2004. Identification of CYP2B6 sequence variants by use of multiplex PCR with allele-specific genotyping. Clin. Chem. 50:13721377.
105. Jain, K. K. 2005. Applications of AmpliChip CYP450. Mol. Diagn. 9:119127.
106. Janneh, O.,, A. Owen,, B. Chandler,, R. C. Hartkoorn,, C. A. Hart,, P. G. Bray,, S. A. Ward,, D. J. Back, and, S. H. Khoo. 2005. Modulation of the intracellular accumulation of saquinavir in peripheral blood mononuclear cells by inhibitors of MRP1, MRP2, P-gp and BCRP. AIDS 19:20972102.
107. Janvilisri, T.,, S. Shahi,, H. Venter,, L. Balakrishnan, and, H. W. van Veen. 2005. Arginine-482 is not essential for transport of antibiotics, primary bile acids and unconjugated sterols by the human breast cancer resistance protein (ABCG2). Biochem. J. 385:419426.
108. Jinno, H.,, T. Tanaka-Kagawa,, A. Ohno,, Y. Makino,, E. Matsushima,, N. Hanioka, and, M. Ando. 2003. Functional characterization of cytochrome P450 2B6 allelic variants. Drug Metab. Dispos. 31:398403.
109. Josephson, F.,, A. Allqvist,, M. Janabi,, J. Sayi,, E. Aklillu,, M. Jande,, M. Mahindi,, J. Burhenne,, Y. Bottiger,, L. L. Gustafsson,, W. E. Haefeli, and, L. Bertilsson. 2007. CYP3A5 genotype has an impact on the metabolism of the HIV protease inhibitor saquinavir. Clin. Pharmacol. Ther. 81:708712.
110. Jounaidi, Y.,, V. Hyrailles,, L. Gervot, and, P. Maurel. 1996. Detection of CYP3A5 allelic variant: a candidate for the polymorphic expression of the protein? Biochem. Biophys. Res. Commun. 221:466470.
111. Jung, N.,, C. Lehmann,, A. Rubbert,, M. Knispel,, P. Hartmann,, J. van Lunzen,, H. J. Stellbrink,, G. Faetkenheuer, and, D. Taubert. 2008. Relevance of the organic cation transporters 1 and 2 for antiretroviral drug therapy in human immunodeficiency virus infection. Drug Metab. Dispos. 36:16161623.
112. Kerb, R. 2006. Implications of genetic polymorphisms in drug transporters for pharmacotherapy. Cancer Lett. 234:433.
113. Kidd, R. S.,, T. B. Curry,, S. Gallagher,, T. Edeki,, J. Blaisdell, and, J. A. Goldstein. 2001. Identification of a null allele of CYP2C9 in an African-American exhibiting toxicity to phenytoin. Pharmacogenetics 11:803808.
114. Kim, R. B. 2006. Transporters and drug discovery: why, when, and how. Mol. Pharm. 3:2632.
115. Kim, R. B.,, B. F. Leake,, E. F. Choo,, G. K. Dresser,, S. V. Kubba,, U. I. Schwarz,, A. Taylor,, H. G. Xie,, J. McKinsey,, S. Zhou,, L. B. Lan,, J. D. Schuetz,, E. G. Schuetz, and, G. R. Wilkinson. 2001. Identification of functionally variant MDR1 alleles among European Americans and African Americans. Clin. Pharmacol. Ther. 70:189199.
116. Kim, R. B.,, C. Wandel,, B. Leake,, M. Cvetkovic,, M. F. Fromm,, P. J. Dempsey,, M. M. Roden,, F. Belas,, A. K. Chaudhary,, D. M. Roden,, A. J. Wood, and, G. R. Wilkinson. 1999. Interrelationship between substrates and inhibitors of human CYP3A and P-glycoprotein. Pharm. Res. 16:408414.
117. Kim, R. B.,, and G. R. Wilkinson. 2001. Pharmacogenetics of drug transporters, p. 81-108. In W. Kalow,, U. A. Meyer, and, R. F. Tyndale (ed.), Pharmacogenomics. Marcel Dekker, Inc., New York, NY.
118. Kimura, S.,, M. Umeno,, R. C. Skoda,, U. A. Meyer, and, F. J. Gonzalez. 1989. The human debrisoquine 4-hydroxylase (CYP2D) locus: sequence and identification of the polymorphic CYP2D6 gene, a related gene, and a pseudogene. Am. J. Hum. Genet. 45:889904.
119. King, B. P.,, T. I. Khan,, G. P. Aithal,, F. Kamali, and, A. K. Daly. 2004. Upstream and coding region CYP2C9 polymorphisms: correlation with warfarin dose and metabolism. Pharmacogenetics 14:813822.
120. King, B. P.,, J. B. Leathart,, E. Mutch,, F. M. Williams, and, A. K. Daly. 2003. CYP3A5 phenotype-genotype correlations in a British population. Br. J. Clin. Pharmacol. 55:625629.
121. Kirchheiner, J. 2008. CYP2D6 phenotype prediction from genotype: which system is the best? Clin. Pharmacol. Ther. 83:225227.
122. Kirchheiner, J.,, C. Klein,, I. Meineke,, J. Sasse,, U. M. Zanger,, T. E. Mürdter,, I. Roots, and, J. Brockmöller. 2003. Bupropion and 4-OH-bupropion pharmacokinetics in relation to genetic polymorphisms in CYP2B6. Pharmacogenetics 13:619626.
123. Koepsell, H.,, B. M. Schmitt, and, V. Gorboulev. 2003. Organic cation transporters. Rev. Physiol. Biochem. Pharmacol. 150:3690.
124. König, J.,, A. Seithel,, U. Gradhand, and, M. F. Fromm. 2006. Pharmacogenomics of human OATP transporters. Naunyn Schmiedebergs Arch. Pharmacol. 372:432443.
125. Kubota, T.,, K. Chiba, and, T. Ishizaki. 1996. Genotyping of S-mephenytoin 4′-hydroxylation in an extended Japanese population. Clin. Pharmacol. Ther. 60:661666.
126. Kuehl, P.,, J. Zhang,, Y. Lin,, J. Lamba,, M. Assem,, J. Schuetz,, P. B. Watkins,, A. Daly,, S. A. Wrighton,, S. D. Hall,, P. Maurel,, M. Relling,, C. Brimer,, K. Yasuda,, R. Venkataramanan,, S. Strom,, K. Thummel,, M. S. Boguski, and, E. Schuetz. 2001. Sequence diversity in CYP3A promoters and characterization of the genetic basis of polymorphic CYP3A5 expression. Nat. Genet. 27:383391.
127. Lamba, J. K.,, Y. S. Lin,, E. G. Schuetz, and, K. E. Thummel. 2002. Genetic contribution to variable human CYP3A-mediated metabolism. Adv. Drug Deliv. Rev. 54:12711294.
128. Lamba, J. K.,, Y. S. Lin,, K. Thummel,, A. Daly,, P. B. Watkins,, S. Strom,, J. Zhang, and, E. G. Schuetz. 2002. Common allelic variants of cytochrome P4503A4 and their prevalence in different populations. Pharmacogenetics 12:121132.
129. Lamba, V.,, J. Lamba,, K. Yasuda,, S. Strom,, J. Davila,, M. L. Hancock,, J. D. Fackenthal,, P. K. Rogan,, B. Ring,, S. A. Wrighton, and, E. G. Schuetz. 2003. Hepatic CYP2B6 expression: gender and ethnic differences and relationship to CYP2B6 genotype and CAR (constitutive androstane receptor) expression. J. Pharmacol. Exp. Ther. 307:906922.
130. Lang, T.,, K. Klein,, J. Fischer,, A. K. Nüssler,, P. Neuhaus,, U. Hofmann,, M. Eichelbaum,, M. Schwab, and, U. M. Zanger. 2001. Extensive genetic polymorphism in the human CYP2B6 gene with impact on expression and function in human liver. Pharmacogenetics 11:399415.
131. Lang, T.,, K. Klein,, T. Richter,, A. Zibat,, R. Kerb,, M. Eichelbaum,, M. Schwab, and, U. M. Zanger. 2004. Multiple novel nonsynonymous CYP2B6 gene polymorphisms in Caucasians: demonstration of phenotypic null alleles. J. Pharmacol. Exp. Ther. 311:3443.
132. Lee, A. M.,, C. Jepson,, E. Hoffmann,, L. Epstein,, L. W. Hawk,, C. Lerman, and, R. F. Tyndale. 2007. CYP2B6 genotype alters abstinence rates in a bupropion smoking cessation trial. Biol. Psychiatry 62:635641.
133. Lee, S. J.,, K. A. Usmani,, B. Chanas,, B. Ghanayem,, T. Xi,, E. Hodgson,, H. W. Mohrenweiser, and, J. A. Goldstein. 2003. Genetic findings and functional studies of human CYP3A5 single nucleotide polymorphisms in different ethnic groups. Pharmacogenetics 13:461472.
134. Leschziner, G. D.,, T. Andrew,, M. Pirmohamed, and, M. R. Johnson. 2007. ABCB1 genotype and PGP expression, function and therapeutic drug response: a critical review and recommendations for future research. Pharmacogenomics J. 7:154179.
135. Letourneau, I. J.,, R. G. Deeley, and, S. P. Cole. 2005. Functional characterization of non-synonymous single nucleotide polymorphisms in the gene encoding human multidrug resistance protein 1 (MRP1/ABCC1). Pharmacogenet. Genomics 15:647657.
136. Li, A. P.,, D. L. Kaminski, and, A. Rasmussen. 1995. Substrates of human hepatic cytochrome P450 3A4. Toxicology 104:18.
137. Lin, Y. S.,, A. L. Dowling,, S. D. Quigley,, F. M. Farin,, J. Zhang,, J. Lamba,, E. G. Schuetz, and, K. E. Thummel. 2002. Co-regulation of CYP3A4 and CYP3A5 and contribution to hepatic and intestinal midazolam metabolism. Mol. Pharmacol. 62:162172.
138. Liu, T. C.,, S. F. Lin,, T. P. Chen, and, J. G. Chang. 2002. Polymorphism analysis of CYP3A5 in myeloid leukemia. Oncol. Rep. 9:327329.
139. Liu, Y. T.,, H. P. Hao,, C. X. Liu,, G. J. Wang, and, H. G. Xie. 2007. Drugs as CYP3A probes, inducers, and inhibitors. Drug Metab. Rev. 39:699721.
140. London, S. J.,, A. K. Daly,, J. B. Leathart,, W. C. Navidi, and, J. R. Idle. 1996. Lung cancer risk in relation to the CYP2C9*1/CYP2C9*2 genetic polymorphism among African-Americans and Caucasians in Los Angeles County, California. Pharmacogenetics 6:527533.
141. London, S. J.,, T. Sullivan-Klose,, A. K. Daly, and, J. R. Idle. 1997. Lung cancer risk in relation to the CYP2C9 genetic polymorphism among Caucasians in Los Angeles County. Pharmacogenetics 7:401404.
142. Maekawa, K.,, H. Fukushima-Uesaka,, M. Tohkin,, R. Hasegawa,, H. Kajio,, N. Kuzuya,, K. Yasuda,, M. Kawamoto,, N. Kamatani,, K. Suzuki,, T. Yanagawa,, Y. Saito, and, J. Sawada. 2006. Four novel defective alleles and comprehensive haplotype analysis of CYP2C9 in Japanese. Pharmacogenet. Genomics 16:497514.
143. Margaglione, M.,, D. Colaizzo,, G. D’Andrea,, V. Brancaccio,, A. Ciampa,, E. Grandone, and, G. Di Minno. 2000. Genetic modulation of oral anticoagulation with warfarin. Thromb. Haemost. 84:775778.
144. Marzolini, C.,, R. G. Tirona, and, R. B. Kim. 2004. Pharmacogenomics of the OATP and OAT families. Pharmacogenomics 5:273282.
145. Mehlotra, R. K.,, M. J. Bockarie, and, P. A. Zimmerman. 2007. CYP2B6 983T>C polymorphism is prevalent in West Africa but absent in Papua New Guinea: implications for HIV/AIDS treatment. Br. J. Clin. Pharmacol. 64:391395.
146. Mehlotra, R. K.,, M. N. Ziats,, M. J. Bockarie, and, P. A. Zimmerman. 2006. Prevalence of CYP2B6 alleles in malaria-endemic populations of West Africa and Papua New Guinea. Eur. J. Clin. Pharmacol. 62:267275.
147. Merino, G.,, A. I. Alvarez,, M. M. Pulido,, A. J. Molina,, A. H. Schinkel, and, J. G. Prieto. 2006. Breast cancer resistance protein (BCRP/ABCG2) transports fluoroquinolone antibiotics and affects their oral availability, pharmacokinetics, and milk secretion. Drug Metab. Dispos. 34:690695.
148. Merino, G.,, J. W. Jonker,, E. Wagenaar,, A. E. van Herwaarden, and, A. H. Schinkel. 2005. The breast cancer resistance protein (BCRP/ABCG2) affects pharmacokinetics, hepatobiliary excretion, and milk secretion of the antibiotic nitrofurantoin. Mol. Pharmacol. 67:17581764.
149. Miners, J. O.,, and D. J. Birkett. 1998. Cytochrome P4502C9: an enzyme of major importance in human drug metabolism. Br. J. Clin. Pharmacol. 45:525538.
150. Mirghani, R. A.,, J. Sayi,, E. Aklillu,, A. Allqvist,, M. Jande,, A. Wennerholm,, J. Eriksen,, V. M. Herben,, B. C. Jones,, L. L. Gustafsson, and, L. Bertilsson. 2006. CYP3A5 genotype has significant effect on quinine 3-hydroxylation in Tanzanians, who have lower total CYP3A activity than a Swedish population. Pharmacogenet. Genomics 16:637645.
151. Morita, J.,, K. Kobayashi,, A. Wanibuchi,, M. Kimura,, S. Irie,, T. Ishizaki, and, K. Chiba. 2004. A novel single nucleotide polymorphism (SNP) of the CYP2C19 gene in a Japanese subject with lowered capacity of mephobarbital 4′-hydroxylation. Drug Metab. Pharmacokinet. 19:236238.
152. Mouly, S. J.,, C. Matheny,, M. F. Paine,, G. Smith,, J. Lamba,, V. Lamba,, S. N. Pusek,, E. G. Schuetz,, P. W. Stewart, and, P. B. Watkins. 2005. Variation in oral clearance of saquinavir is predicted by CYP3A5*1 genotype but not by enterocyte content of cytochrome P450 3A5. Clin. Pharmacol. Ther. 78:605618.
153. Murayama, N.,, T. Nakamura,, M. Saeki,, A. Soyama,, Y. Saito,, K. Sai,, S. Ishida,, O. Nakajima,, M. Itoda,, Y. Ohno,, S. Ozawa, and, J. Sawada. 2002. CYP3A4 gene polymorphisms influence testosterone 6βx-hydroxylation. Drug Metab. Pharmacokinet. 17:150156.
154. Nakajima, M.,, S. Komagata,, Y. Fujiki,, Y. Kanada,, H. Ebi,, K. Itoh,, H. Mukai,, T. Yokoi, and, H. Minami. 2007. Genetic polymorphisms of CYP2B6 affect the pharmacokinetics/pharmacodynamics of cyclophosphamide in Japanese cancer patients. Pharmacogenet. Genomics 17:431445.
155. Nakamoto, K.,, J. R. Kidd,, R. D. Jenison,, C. D. Klaassen,, Y. J. Wan,, K. K. Kidd, and, X. B. Zhong. 2007. Genotyping and haplotyping of CYP2C19 functional alleles on thin-film biosensor chips. Pharmacogenet. Genomics 17:103114.
156. Nasu, K.,, T. Kubota, and, T. Ishizaki. 1997. Genetic analysis of CYP2C9 polymorphism in a Japanese population. Pharmacogenetics 7:405409.
157. Nelson, D. R.,, L. Koymans,, T. Kamataki,, J. J. Stegeman,, R. Feyereisen,, D. J. Waxman,, M. R. Waterman,, O. Gotoh,, M. J. Coon,, R. W. Estabrook,, I. C. Gunsalus, and, D. W. Nebert. 1996. P450 superfamily: update on new sequences, gene mapping, accession numbers and nomenclature. Pharmacogenetics 6:142.
158. Nelson, D. R.,, D. C. Zeldin,, S. M. Hoffman,, L. J. Maltais,, H. M. Wain, and, D. W. Nebert. 2004. Comparison of cytochrome P450 (CYP) genes from the mouse and human genomes, including nomenclature recommendations for genes, pseudogenes and alternativesplice variants. Pharmacogenetics 14:118.
159. Nolan, D.,, E. Phillips, and, S. Mallal. 2006. Efavirenz and CYP2B6 polymorphism: implications for drug toxicity and resistance. Clin. Infect. Dis. 42:408410.
160. Nowak, M. P.,, E. M. Sellers, and, R. F. Tyndale. 1998. Canadian Native Indians exhibit unique CYP2A6 and CYP2C19 mutant allele frequencies. Clin. Pharmacol. Ther. 64:378383.
161. Ozdemir, V.,, W. Kalow,, B. K. Tang,, A. D. Paterson,, S. E. Walker,, L. Endrenyi, and, A. D. Kashuba. 2000. Evaluation of the genetic component of variability in CYP3A4 activity: a repeated drug administration method. Pharmacogenetics 10:373388.
162. Paine, M. F.,, H. L. Hart,, S. S. Ludington,, R. L. Haining,, A. E. Rettie, and, D. C. Zeldin. 2006. The human intestinal cytochrome P450 “pie.” Drug Metab. Dispos. 34:880886.
163. Pirmohamed, M.,, A. Alfirevic,, J. Vilar,, A. Stalford,, E. G. Wilkins,, E. Sim, and, B. K. Park. 2000. Association analysis of drug metabolizing enzyme gene polymorphisms in HIV-positive patients with co-trimoxazole hypersensitivity. Pharmacogenetics 10:705713.
164. Plummer, S. J.,, D. V. Conti,, P. L. Paris,, A. P. Curran,, G. Casey, and, J. S. Witte. 2003. CYP3A4 and CYP3A5 genotypes, haplotypes, and risk of prostate cancer. Cancer Epidemiol. Biomarkers Prev. 12:928932.
165. Rasmussen, H. B.,, and T. Werge. 2008. Advice on the genotyping of CYP2C19: comments on a recent article. Pharmacogenet. Genomics 18:647648.
166. Reid, G.,, P. Wielinga,, N. Zelcer,, M. de Haas,, L. van Deemter,, J. Wijnholds,, J. Balzarini, and, P. Borst. 2003. Characterization of the transport of nucleoside analog drugs by the human multidrug resistance proteins MRP4 and MRP5. Mol. Pharmacol. 63:10941103.
167. Rendic, S.,, and F. J. Di Carlo. 1997. Human cytochrome P450 enzymes: a status report summarizing their reactions, substrates, inducers, and inhibitors. Drug Metab. Rev. 29:413580.
168. Rizwan, A. N.,, and G. Burckhardt. 2007. Organic anion transporters of the SLC22 family: biopharmaceutical, physiological, and pathological roles. Pharm. Res. 24:450470.
169. Rodriguez-Novoa, S.,, P. Barreiro,, A. Rendon,, I. Jimenez-Nacher,, J. Gonzalez-Lahoz, and, V. Soriano. 2005. Influence of 516G>T polymorphisms at the gene encoding the CYP450-2B6 isoenzyme on efavirenz plasma concentrations in HIV-infected subjects. Clin. Infect. Dis. 40:13581361.
170. Rogan, P. K.,, S. Svojanovsky, and, J. S. Leeder. 2003. Information theory-based analysis of CYP2C19, CYP2D6 and CYP3A5 splicing mutations. Pharmacogenetics 13:207218.
171. Rohrbacher, M.,, A. Kirchhof,, G. Geisslinger, and, J. Lotsch. 2006. Pyrosequencing-based screening for genetic polymorphisms in cytochrome P450 2B6 of potential clinical relevance. Pharmacogenomics 7:9951002.
172. Ronaghi, M.,, S. Karamohamed,, B. Pettersson,, M. Uhlen, and, P. Nyren. 1996. Real-time DNA sequencing using detection of pyrophosphate release. Anal. Biochem. 242:8489.
173. Ross, P.,, L. Hall,, I. Smirnov, and, L. Haff. 1998. High level multiplex genotyping by MALDI-TOF mass spectrometry. Nat. Biotechnol. 16:13471351.
174. Rotger, M.,, H. Tegude,, S. Colombo,, M. Cavassini,, H. Furrer,, L. Décosterd,, J. Blievernicht,, T. Saussele,, H. F. Günthard,, M. Schwab,, M. Eichelbaum,, A. Telenti, and, U. M. Zanger. 2007. Predictive value of known and novel alleles of CYP2B6 for efavirenz plasma concentrations in HIV-infected individuals. Clin. Pharmacol. Ther. 81:557566.
175. Rotger, M.,, and A. Telenti. 2008. Optimizing efavirenz treatment: CYP2B6 genotyping or therapeutic drug monitoring? Eur. J. Clin. Pharmacol. 64:335336.
176. Rudberg, I.,, B. Mohebi,, M. Hermann,, H. Refsum, and, E. Molden. 2008. Impact of the ultrarapid CYP2C19*17 allele on serum concentration of escitalopram in psychiatric patients. Clin. Pharmacol. Ther. 83:322327.
177. Saitoh, A.,, E. Sarles,, E. Capparelli,, F. Aweeka,, A. Kovacs,, S. K. Burchett,, A. Wiznia,, S. Nachman,, T. Fenton, and, S. A. Spector. 2007. CYP2B6 genetic variants are associated with nevirapine pharmacokinetics and clinical response in HIV-1-infected children. AIDS 21:21912199.
178. Saitoh, A.,, K. K. Singh,, C. A. Powell,, T. Fenton,, C. V. Fletcher,, R. Brundage,, S. Starr, and, S. A. Spector. 2005. An MDR1-3435 variant is associated with higher plasma nelfinavir levels and more rapid virologic response in HIV-1 infected children. AIDS 19:371380.
179. Sata, F.,, A. Sapone,, G. Elizondo,, P. Stocker,, V. P. Miller,, W. Zheng,, H. Raunio,, C. L. Crespi, and, F. J. Gonzalez. 2000. CYP3A4 allelic variants with amino acid substitutions in exons 7 and 12: evidence for an allelic variant with altered catalytic activity. Clin. Pharmacol. Ther. 67:4856.
180. Schaeffeler, E.,, M. Eichelbaum,, U. Brinkmann,, A. Penger,, S. Asante-Poku,, U. M. Zanger, and, M. Schwab. 2001. Frequency of C3435T polymorphism of MDR1 gene in African people. Lancet 358:383384.
181. Schuetz, J. D.,, D. T. Molowa, and, P. S. Guzelian. 1989. Characterization of a cDNA encoding a new member of the glucocorticoid-responsive cytochromes P450 in human liver. Arch. Biochem. Biophys. 274:355365.
182. Shih, P. S.,, and J. D. Huang. 2002. Pharmacokinetics of midazolam and 1′-hydroxymidazolam in Chinese with different CYP3A5 genotypes. Drug Metab. Dispos. 30:14911496.
183. Shimada, T.,, H. Yamazaki,, M. Mimura,, Y. Inui, and, F. P. Guengerich. 1994. Interindividual variations in human liver cytochrome P-450 enzymes involved in the oxidation of drugs, carcinogens and toxic chemicals: studies with liver microsomes of 30 Japanese and 30 Caucasians. J. Pharmacol. Exp. Ther. 270:414423.
184. Shintani, M.,, I. Ieiri,, K. Inoue,, K. Mamiya,, H. Ninomiya,, N. Tashiro,, S. Higuchi, and, K. Otsubo. 2001. Genetic polymorphisms and functional characterization of the 5′-flanking region of the human CYP2C9 gene: in vitro and in vivo studies. Clin. Pharmacol. Ther. 70:175182.
185. Si, D.,, Y. Guo,, Y. Zhang,, L. Yang,, H. Zhou, and, D. Zhong. 2004. Identification of a novel variant CYP2C9 allele in Chinese. Pharmacogenetics 14:465469.
186. Sim, S. C.,, C. Risinger,, M. L. Dahl,, E. Aklillu,, M. Christensen,, L. Bertilsson, and, M. Ingelman-Sundberg. 2006. A common novel CYP2C19 gene variant causes ultrarapid drug metabolism relevant for the drug response to proton pump inhibitors and antidepressants. Clin. Pharmacol. Ther. 79:103113.
187. Solus, J. F.,, B. J. Arietta,, J. R. Harris,, D. P. Sexton,, J. Q. Steward,, C. McMunn,, P. Ihrie,, J. M. Mehall,, T. L. Edwards, and, E. P. Dawson. 2004. Genetic variation in eleven phase I drug metabolism genes in an ethnically diverse population. Pharmacogenomics 5:895931.
188. Song, P.,, N. Dirks, and, A. O. Gaber. 2002. Detection of CYP3A5*3 and *6 using real-time PCR. Clin. Pharmacol. Ther. 71:P103.
189. Spurr, N. K.,, A. C. Gough,, K. Stevenson, and, C. R. Wolf. 1989. The human cytochrome P450 CYP3 locus: assignment to chromosome 7q22-qter. Hum. Genet. 81:171174.
190. Stubbins, M. J.,, L. W. Harries,, G. Smith,, M. H. Tarbit, and, C. R. Wolf. 1996. Genetic analysis of the human cytochrome P450 CYP2C9 locus. Pharmacogenetics 6:429439.
191. Sullivan-Klose, T. H.,, B. I. Ghanayem,, D. A. Bell,, Z. Y. Zhang,, L. S. Kaminsky,, G. M. Shenfield,, J. O. Miners,, D. J. Birkett, and, J. A. Goldstein. 1996. The role of the CYP2C9-Leu359 allelic variant in the tolbutamide polymorphism. Pharmacogenetics 6:341349.
192. Takakubo, F.,, A. Kuwano, and, I. Kondo. 1996. Evidence that poor metabolizers of (S)-mephenytoin could be identified by haplotypes of CYP2C19 in Japanese. Pharmacogenetics 6:265267.
193. Tanigawara, Y.,, N. Aoyama,, T. Kita,, K. Shirakawa,, F. Komada,, M. Kasuga, and, K. Okumura. 1999. CYP2C19 genotype-related efficacy of omeprazole for the treatment of infection caused by Helicobacter pylori. Clin. Pharmacol. Ther. 66:528534.
194. Taube, J.,, D. Halsall, and, T. Baglin. 2000. Influence of cytochrome P-450 CYP2C9 polymorphisms on warfarin sensitivity and risk of over-anticoagulation in patients on long-term treatment. Blood 96:18161819.
195. Telenti, A.,, and U. M. Zanger. 2008. Pharmacogenetics of anti-HIV drugs. Annu. Rev. Pharmacol. Toxicol. 48:227256.
196. Thervet, E.,, D. Anglicheau,, B. King,, M. H. Schlageter,, B. Cassinat,, P. Beaune,, C. Legendre, and, A. K. Daly. 2003. Impact of cytochrome p450 3A5 genetic polymorphism on tacrolimus doses and concentration-to-dose ratio in renal transplant recipients. Transplantation 76:12331235.
197. Thummel, K. E.,, and G. R. Wilkinson. 1998. In vitro and in vivo drug interactions involving human CYP3A. Annu. Rev. Pharmacol. Toxicol. 38:389430.
198. Tirona, R. G.,, B. F. Leake,, A. W. Wolkoff, and, R. B. Kim. 2003. Human organic anion transporting polypeptide-C (SLC21A6) is a major determinant of rifampin-mediated pregnane X receptor activation. J. Pharmacol. Exp. Ther. 304:223228.
199. Tsuchiya, K.,, H. Gatanaga,, N. Tachikawa,, K. Teruya,, Y. Kikuchi,, M. Yoshino,, T. Kuwahara,, T. Shirasaka,, S. Kimura, and, S. Oka. 2004. Homozygous CYP2B6 *6 (Q172H and K262R) correlates with high plasma efavirenz concentrations in HIV-1 patients treated with standard efavirenz-containing regimens. Biochem. Biophys. Res. Commun. 319:13221326.
200. Tsuneoka, Y.,, K. Fukushima,, Y. Matsuo,, Y. Ichikawa, and, Y. Watanabe. 1996. Genotype analysis of the CYP2C19 gene in the Japanese population. Life Sci. 59:17111715.
201. van Schaik, R. H.,, I. P. van der Heiden,, J. N. van den Anker, and, J. Lindemans. 2002. CYP3A5 variant allele frequencies in Dutch Caucasians. Clin. Chem. 48:16681671. (Erratum, 49:528, 2003.)
202. Veenstra, D. L.,, D. K. Blough,, M. K. Higashi,, F. M. Farin,, S. Srinouanprachan,, M. J. Rieder, and, A. E. Rettie. 2005. CYP2C9 haplotype structure in European American warfarin patients and association with clinical outcomes. Clin. Pharmacol. Ther. 77:353364.