Genome-wide association study of plasma efavirenz pharmacokinetics in AIDS Clinical Trials Group protocols implicates several CYP2B6 variants

Pharmacogenetics and Genomics

Volumn 22, Issue 12, 2012, Pages 858-867

  Holzinger, Emily R ^a   Grady, Benjamin ^a   Ritchie, Marylyn D ^c   Ribaudo, Heather J ^d   Acosta, Edward P ^g   Morse, Gene D ^h   Gulick, Roy M ⁱ   Robbins, Gregory K ^e   Clifford, David B ^j   Daar, Eric S ^k   McLaren, Paul ^f   Haas, David W ^a,b  

^a VANDERBILT UNIVERSITY MEDICAL CENTER   (United States)

^b VANDERBILT UNIVERSITY SCHOOL OF MEDICINE   (United States)

^c PENNSYLVANIA STATE UNIVERSITY   (United States)

^d HARVARD SCHOOL OF PUBLIC HEALTH   (United States)

^e HARVARD MEDICAL SCHOOL   (United States)

^f BROAD INSTITUTE OF MIT AND HARVARD   (United States)

^g University of Alabama at Birmingham   (United States)

^h UNIVERSITY AT BUFFALO   (United States)

ⁱ WEILL CORNELL MEDICAL COLLEGE   (United States)

^j WASHINGTON UNIVERSITY SCHOOL OF MEDICINE   (United States)

^k HARBOR UCLA MEDICAL CENTER   (United States)

more..

Author keywords

CYP2B6; efavirenz; HIV; pharmacogenomics; pharmacokinetics

Indexed keywords

CYTOCHROME P450 2B6; DNA; EFAVIRENZ;

ARTICLE; CLINICAL PROTOCOL; CYP2B6 GENE; DRUG BLOOD LEVEL; DRUG METABOLISM; FEMALE; GENE; GENE LINKAGE DISEQUILIBRIUM; GENETIC ASSOCIATION; GENETIC VARIABILITY; GENOTYPE; GENOTYPE PHENOTYPE CORRELATION; HUMAN; MAJOR CLINICAL STUDY; MALE; PHARMACOGENOMICS; PRIORITY JOURNAL; SINGLE NUCLEOTIDE POLYMORPHISM;

EID: 84870335137     PISSN: 17446872     EISSN: 17446880     Source Type: Journal    
DOI: 10.1097/FPC.0b013e32835a450b     Document Type: Article

References (40)

1. Gulick RM, Ribaudo HJ, Shikuma CM, Lalama C, Schackman BR, Meyer WA, et al. Three-vs four-drug antiretroviral regimens for the initial treatment of HIV-1 infection: a randomized controlled trial. JAMA 2006; 296:769-781. (Pubitemid 44223101)
2. Clifford DB, Evans S, Yang Y, Acosta EP, Goodkin K, Tashima K, et al. Impact of efavirenz on neuropsychological performance and symptoms in HIV-infected individuals. Ann Intern Med 2005; 143:714-721.
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. (Pubitemid 36734384)
4. 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. (Pubitemid 40065906)
5. Tsuchiya K, Gatanaga H, Tachikawa N, Teruya K, Kikuchi Y, Yoshino M, et al. Homozygous CYP2B66 (Q172H and K262R) correlates with high plasma efavirenz concentrations in HIV-1 patients treated with standard efavirenz-containing regimens. Biochem Biophys Res Commun 2004; 319:1322-1326. (Pubitemid 38759555)
6. Haas DW, Smeaton LM, Shafer RW, Robbins GK, Morse GD, Labbe L, et al. Pharmacogenetics of long-term responses to antiretroviral regimens containing efavirenz and/or nelfinavir: an Adult AIDS Clinical Trials Group study. J Infect Dis 2005; 192:1931-1942. (Pubitemid 41681891)
7. Rotger M, Colombo S, Furrer H, Bleiber G, Buclin T, Lee BL, et al. Influence of CYP2B6 polymorphism on plasma and intracellular concentrations and toxicity of efavirenz and nevirapine in HIV-infected patients. Pharmacogenet Genomics 2005; 15:1-5. (Pubitemid 43205520)
8. Rodriguez-Novoa S, Barreiro P, Rendon A, Jimenez-Nacher I, Gonzalez-Lahoz J, Soriano V. 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; 40:1358-1361. (Pubitemid 40570249)
9. dbSNP. Short genetic variations. Available at: http://www.ncbi.nlm.nih. gov/projects/SNP/[Accessed 5 January 2012].
10. Barrett JS, Joshi AS, Chai M, Ludden TM, Fiske WD, Pieniaszek HJ Jr. Population pharmacokinetic meta-analysis with efavirenz. Int J Clin Pharmacol Ther 2002; 40:507-519. (Pubitemid 35331935)
11. Pfister M, Labbe L, Hammer SM, Mellors J, Bennett KK, Rosenkranz S, Sheiner LB, et al. Population pharmacokinetics and pharmacodynamics of efavirenz, nelfinavir, and indinavir: Adult AIDS Clinical Trial Group Study 398. Antimicrob Agents Chemother 2003; 47:130-137. (Pubitemid 36070353)
12. Wang J, Sonnerborg A, Rane A, Josephson F, Lundgren S, Stahle L, Ingelman-Sundberg M, 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.
13. Wyen C, Hendra H, Vogel M, Hoffmann C, Knechten H, Brockmeyer NH, et al. Impact of CYP2B6 983T > C polymorphism on non-nucleoside reverse transcriptase inhibitor plasma concentrations in HIV-infected patients. J Antimicrob Chemother 2008; 61:914-918. (Pubitemid 351436194)
14. Ribaudo HJ, Liu H, Schwab M, Schaeffeler E, Eichelbaum M, Motsinger-Reif AA, et al. Effect of CYP2B6, ABCB1, and CYP3A5 polymorphisms on efavirenz pharmacokinetics and treatment response: an AIDS Clinical Trials Group study. J Infect Dis 2010; 202:717-722.
15. Hofmann MH, Blievernicht JK, Klein K, Saussele T, Schaeffeler E, Schwab M, Zanger UM. Aberrant splicing caused by single nucleotide polymorphism c.516G > T [Q172H], a marker of CYP2B66, is responsible for decreased expression and activity of CYP2B6 in liver. J Pharmacol Exp Ther 2008; 325:284-292. (Pubitemid 351439175)
16. 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. (Pubitemid 41666768)
17. Rotger M, Colombo S, Cavassini M, Furrer H, Elzi L, Ganthard H, et al. Genetic variability of CYP2B6 in individuals with extremely high efavirenz plasma concentrations. Presented at 13th Conference on Retroviruses and Opportunistic Infections, February 2006; Denver, CO; abstract 572 2006.
18. 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. (Pubitemid 46454205)
19. Rotger M, Saumoy M, Zhang K, Flepp M, Sahli R, Decosterd L, Telenti A, et al. Partial deletion of CYP2B6 owing to unequal crossover with CYP2B7. Pharmacogenet Genomics 2007; 17:885-890. (Pubitemid 47462302)
20. Di Iulio J, Fayet A, Arab-Alameddine M, Rotger M, Lubomirov R, Cavassini M, et al. In vivo analysis of efavirenz metabolism in individuals with impaired CYP2A6 function. Pharmacogenet Genomics 2009; 19:300-309.
21. Kwara A, Lartey M, Sagoe KW, Kenu E, Court MH. CYP2B6, CYP2A6 and UGT2B7 genetic polymorphisms are predictors of efavirenz mid-dose concentration in HIV-infected patients. AIDS 2009; 23:2101-2106.
22. Arab-Alameddine M, Di Iulio J, Buclin T, Rotger M, Lubomirov R, Cavassini M, et al. Pharmacogenetics-based population pharmacokinetic analysis of efavirenz in HIV-1-infected individuals. Clin Pharmacol Ther 2009; 85:485-494.
23. Wyen C, Hendra H, Siccardi M, Platten M, Jaeger H, Harrer T, et al. Cytochrome P450 2B6 (CYP2B6) and constitutive androstane receptor (CAR) polymorphisms are associated with early discontinuation of efavirenz-containing regimens. J Antimicrob Chemother 2011; 66:2092-2098.
24. Robbins GK, De GV, Shafer RW, Smeaton LM, Snyder SW, Pettinelli C, et al. Comparison of sequential three-drug regimens as initial therapy for HIV-1 infection. N Engl J Med 2003; 349:2293-2303. (Pubitemid 37509737)
25. Shafer RW, Smeaton LM, Robbins GK, De Gruttola V, Snyder SW, D'Aquila RT, et al. Comparison of four-drug regimens and pairs of sequential three-drug regimens as initial therapy for HIV-1 infection. N Engl J Med 2003; 349:2304-2315. (Pubitemid 37509738)
26. Sax PE, Tierney C, Collier AC, Fischl MA, Mollan K, Peeples L, et al. Abacavir-lamivudine versus tenofovir-emtricitabine for initial HIV-1 therapy. N Engl J Med 2009; 361:2230-2240.
27. Daar ES, Tierney C, Fischl MA, Sax PE, Mollan K, Budhathoki C, et al. Atazanavir plus ritonavir or efavirenz as part of a 3-drug regimen for initial treatment of HIV-1. Ann Intern Med 2011; 154:445-456.
28. Haas DW, Wilkinson GR, Kuritzkes DR, Richman DD, Nicotera J, Mahon LF, et al. A multi-investigator/institutional DNA bank for AIDS-related human genetic studies: AACTG Protocol A5128. HIV Clin Trials 2003; 4:287-300. (Pubitemid 37304432)
29. Pereyra F, Jia X, McLaren PJ, Telenti A, de Bakker PI, Walker BD, et al. The major genetic determinants of HIV-1 control affect HLA class I peptide presentation. Science 2010; 330:1551-1557.
30. SeattleSNPs. Variation discovery resource. Available at: http://pga.gs.washington.edu/[Accessed 5 January 2012].
31. Ensembl Genome Browser. Available at: http://useast.ensembl.org/index. html [Accessed 5 January 2012].
32. Purcell S, Neale B, Todd-Brown K, Thomas L, Ferreira MA, Bender D, et al. PLINK: a tool set for whole-genome association and population-based linkage analyses. Am J Hum Genet 2007; 81:559-575. (Pubitemid 47330214)
33. Price AL, Patterson NJ, Plenge RM, Weinblatt ME, Shadick NA, Reich D. Principal components analysis corrects for stratification in genome-wide association studies. Nat Genet 2006; 38:904-909. (Pubitemid 44141658)
34. Weale ME. Quality control for genome-wide association studies. Methods Mol Biol 2010; 628:341-372.
35. Acosta EP, King Jr. Methods for integration of pharmacokinetic and phenotypic information in the treatment of infection with human immunodeficiency virus. Clin Infect Dis 2003; 36:373-377. (Pubitemid 36169676)
36. Patterson N, Price AL, Reich D. Population structure and eigenanalysis. PLoS Genet 2006; 2:e190.
37. Team RDC. R: a language and environment for statistical computing. Vienna, Austria: R Foundation for Statistical Computing; 2011.
38. Bertrand J, Chou M, Richardson DM. Multiple genetic variants predict steady-state nevirapine clearance in HIV-infected Cambodians. Pharmacogenet Genomics 2012.
39. Lamba V, Lamba J, Yasuda K, Strom S, Davila JC, Hancock M, et al. Hepatic CYP2B6 expression: gender and ethnic differences and relationship to CYP2B6 genotype and CAR expression. J Pharmacol Exp Ther 2003; 307:906-922. (Pubitemid 37494207)
40. 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. (Pubitemid 39287781)