Tribal ethnicity and CYP2B6 genetics in Ugandan and Zimbabwean populations in the UK: Implications for efavirenz dosing in HIV infection

Journal of Antimicrobial Chemotherapy

Volumn 65, Issue 12, 2010, Pages 2614-2619

  Jamshidi, Y ^a   Moreton, M ^a   McKeown, D A ^a   Andrews, S ^b   Nithiyananthan, T ^a   Tinworth, L ^a   Holt, D W ^a   Sadiq, S T ^a,b  

^a ST GEORGE'S UNIVERSITY OF LONDON   (United Kingdom)

^b ST GEORGE'S UNIVERSITY HOSPITALS NHS FOUNDATION TRUST   (United Kingdom)

Author keywords

Antiretrovirals; Bantu; Efavirenz; Genetic diversity; HIV; Nilotic; Pharmacogenetics

Indexed keywords

ANTIRETROVIRUS AGENT; CYTOCHROME P450 2B6; EFAVIRENZ; GENOMIC DNA;

ADULT; AFRICAN AMERICAN; ALLELE; ARTICLE; BLOOD SAMPLING; CLINICAL TRIAL; CONTROLLED STUDY; DRUG BLOOD LEVEL; DRUG METABOLISM; ETHNICITY; EXON; FEMALE; GENE FREQUENCY; GENE SEQUENCE; GENETIC ANALYSIS; GENETIC DIFFERENCE; GENETIC EPIDEMIOLOGY; GENETIC VARIABILITY; GENOTYPE; HAPLOTYPE; HUMAN; HUMAN IMMUNODEFICIENCY VIRUS 1; HUMAN IMMUNODEFICIENCY VIRUS INFECTION; LOSS OF FUNCTION MUTATION; MAJOR CLINICAL STUDY; MALE; MULTICENTER STUDY; PROSPECTIVE STUDY; SINGLE NUCLEOTIDE POLYMORPHISM; UGANDA; UNITED KINGDOM; ZIMBABWE;

ADULT; AFRICAN CONTINENTAL ANCESTRY GROUP; ANTI-HIV AGENTS; ARYL HYDROCARBON HYDROXYLASES; BENZOXAZINES; DOSE-RESPONSE RELATIONSHIP, DRUG; FEMALE; GREAT BRITAIN; HAPLOTYPES; HIV INFECTIONS; HIV-1; HUMANS; MALE; MIDDLE AGED; OXIDOREDUCTASES, N-DEMETHYLATING; POLYMORPHISM, SINGLE NUCLEOTIDE; REVERSE TRANSCRIPTASE INHIBITORS; UGANDA; ZIMBABWE;

EID: 78149477745     PISSN: 03057453     EISSN: 14602091     Source Type: Journal    
DOI: 10.1093/jac/dkq369     Document Type: Article

References (27)

1. Life expectancy of individuals on combination antiretroviral therapy in high-income countries: a collaborative analysis of 14 cohort studies. Antiretroviral Therapy Cohort Collaboration. Lancet 2008; 372: 293-9.
2. Trotta MP, Ammassari A, Melzi S et al. AdICoNA Study Group. Treatment-related factors and highly active antiretroviral therapy adherence. J Acquir Immune Defic Syndr 2002; 31 Suppl 3: 128-31.
3. Marzolini C, Telenti A, Decosterd LA et al. Efavirenz plasma levels can predict treatment failure and central nervous system side effects in HIV-1-infected patients. AIDS 2001; 15:71-5.
4. Desta Z, Saussele T, Ward B et al. Impact of CYP2B6 polymorphism on hepatic efavirenz metabolism in vitro. Pharmacogenomics 2007; 8: 547-58.
5. Ward BA, Gorski JC, Jones DR et al. 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.
6. Arab-Alameddine M, di Iulio J, Buclin T et al. Pharmacogenetics-based population pharmacokinetic analysis of efavirenz in HIV-1-infected individuals. Clin Pharmacol Ther 2009; 85: 485-94.
7. Kwara A, Lartey M, Sagoe KW et al. CYP2B6 (c.516→T) and CYP2A6 (*9B and/or *17) polymorphisms are independent predictors of efavirenz plasma concentrations in HIV-infected patients. Br J Clin Pharmacol 2009; 67: 427-36.
8. 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; 11: 399-415.
9. 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: 2391-400.
10. Hofmann MH, Blievernicht JK, Klein K et al. Aberrant splicing caused by single nucleotide polymorphism c.516G.T [Q172H], a marker of CYP2B6*6, is responsible for decreased expression and activity of CYP2B6 in liver. J Pharmacol Exp Ther 2008; 325: 284-92.
11. Mehlotra RK, Bockarie MJ, Zimmerman PA. CYP2B6 983T.C polymorphism is prevalent in West Africa but absent in Papua New Guinea: implications for HIV/AIDS treatment. Br J Clin Pharmacol 2007; 64: 391-5.
12. 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; 16: 191-8.
13. Lamba V, Lamba J, Yasuda K 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: 906-22.
14. Mehlotra RK, Ziats MN, Bockarie MJ et al. Prevalence of CYP2B6 alleles in malaria-endemic populations of West Africa and Papua New Guinea. Eur J Clin Pharmacol 2006; 62: 267-75.
15. Masimirembwa CM, Hasler JA. Genetic polymorphism of drug metabolising enzymes in African populations: implications for the use of neuroleptics and antidepressants. Brain Res Bull 1997; 44: 561-71.
16. Ethnologue. http://www.ethnologue.com/show_country.asp?name=UG (25 August 2010, date last accessed).
17. Rotger M, Saumoy M, Zhang K et al. Partial deletion of CYP2B6 owing to unequal crossover with CYP2B7. Pharmacogenet Genomics 2007; 17: 885-90.
18. Tsuchiya K, Gatanaga H, Tachikawa N et al. 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 2004; 319: 1322-6.
19. Klein K, Lang T, Saussele T 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: 861-73.
20. 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; 81: 557-66.
21. Kirchheiner J, Klein C, Meineke I et al. Bupropion and 4-OH-bupropion pharmacokinetics in relation to genetic polymorphisms in CYP2B6. Pharmacogenetics 2003; 13: 619-26.
22. Nyakutira C, Roshammar D, Chigutsa E et al. High prevalence of the CYP2B6 516→T(*6) variant and effect on the population pharmacokinetics of efavirenz in HIV/AIDS outpatients in Zimbabwe. Eur J Clin Pharmacol 2008; 64: 357-65.
23. Berniell-Lee G, Calafell F, Bosch E et al. Genetic and demographic implications of the Bantu expansion: insights from human paternal lineages. Mol Biol Evol 2009; 26: 1581-9.
24. Orkin C, Sadiq ST, Rice L et al. Prospective epidemiological study of the prevalence of human leukocyte antigen (HLA)-B5701 in HIV-1-infected UK subjects. HIV Med 2010; 11: 187-92.
25. Mallal S, Nolan D, Witt C et al. Association between presence of HLA-B*5701, HLA-DR7, and HLA-DQ3 and hypersensitivity to HIV-1 reverse-transcriptase inhibitor abacavir. Lancet 2002; 359: 727-32.
26. di Iulio J, Fayet A, Arab-Alameddine M et al. In vivo analysis of efavirenz metabolism in individuals with impaired CYP2A6 function. Pharmacogenet Genomics 2009; 19: 300-9.
27. Carr DF, la Porte CJ, Pirmohamed M et al. Haplotype structure of CYP2B6 and association with plasma efavirenz concentrations in a Chilean HIV cohort. J Antimicrob Chemother 2010; 65: 1889-93.