CYP2B6 983T>C Polymorphism is Prevalent in West Africa but Absent in Papua New Guinea: Implications for HIV/AIDS Treatment

Overview

Journal Br J Clin Pharmacol

Specialty Pharmacology

Date 2007 Mar 30

PMID 17391322

Citations 38

Authors

Rajeev K Mehlotra

Moses J Bockarie

Peter A Zimmerman

Affiliations

Soon will be listed here.

Abstract

Aims: To determine the prevalence of the novel CYP2B6 functional polymorphism 983T>C in Papua New Guinea where HIV/AIDS poses a significant health problem.

Method: We genotyped Papua New Guineans (PNG, n = 174), West Africans (WA, n = 170), and North Americans (NA, n = 361).

Results: The polymorphism was absent in PNG, while its overall frequency was 4.7% in WA. Among NA, the polymorphism was present in African-Americans (7.5%) and Hispanic-Americans (1.1%) but not in Caucasian-Americans and Asian-Americans. Haplotype analysis indicated that 983T>C was present alone as the CYP2B6*18 allele in WA and African-Americans.

Conclusions: Significant interethnic differences occur at the CYP2B6 locus, which may influence treatment outcomes with efavirenz.

Citing Articles

Pharmacogenomics of Chemotherapies for Childhood Cancers in Africa: A Scoping Review.

Katabalo D, Mwita S, Liwa A, Kidenya B, Schroeder K Pharmgenomics Pers Med. 2025; 18:55-69.

PMID: 39968370 PMC: 11834739. DOI: 10.2147/PGPM.S502355.

Pharmacogenetics of Breast Cancer Treatments: A Sub-Saharan Africa Perspective.

Nthontho K, Ndlovu A, Sharma K, Kasvosve I, Hertz D, Paganotti G Pharmgenomics Pers Med. 2022; 15:613-652.

PMID: 35761855 PMC: 9233488. DOI: 10.2147/PGPM.S308531.

Effects of cytochrome P450 2B6 and constitutive androstane receptor genetic variation on Efavirenz plasma concentrations among HIV patients in Kenya.

Ngayo M, Oluka M, Kwena Z, Bulimo W, Okalebo F PLoS One. 2022; 17(3):e0260872.

PMID: 35235559 PMC: 8890732. DOI: 10.1371/journal.pone.0260872.

The Polymorphism and Phenotypic Correlation of Efavirenz-Based Combination Therapy Among the Niger Delta Ethnic Population: Implications in Modern Pharmacogenomics.

Bunu S, Owaba A, Vaikosen E, Ebeshi B Pharmgenomics Pers Med. 2022; 15:45-54.

PMID: 35115810 PMC: 8800862. DOI: 10.2147/PGPM.S345038.

Association of Genetic Variation with Efavirenz and Nevirapine Drug Resistance in HIV-1 Patients from Botswana.

Maseng M, Tawe L, Thami P, Seatla K, Moyo S, Martinelli A Pharmgenomics Pers Med. 2021; 14:335-347.

PMID: 33758532 PMC: 7981136. DOI: 10.2147/PGPM.S289471.

References

Erickson D, Mather G, TRAGER W, Levy R, Keirns J . 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(12):1488-95. View

Mehlotra R, Bockarie M, Zimmerman P . Prevalence of UGT1A9 and UGT2B7 nonsynonymous single nucleotide polymorphisms in West African, Papua New Guinean, and North American populations. Eur J Clin Pharmacol. 2006; 63(1):1-8. PMC: 2577308. DOI: 10.1007/s00228-006-0206-z. View

Ward B, Gorski J, Jones D, Hall S, Flockhart D, 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(1):287-300. DOI: 10.1124/jpet.103.049601. View

Tsuchiya K, Gatanaga H, Tachikawa N, Teruya K, Kikuchi Y, Yoshino M . 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(4):1322-6. DOI: 10.1016/j.bbrc.2004.05.116. View

Lang T, Klein K, Richter T, Zibat A, Kerb R, Eichelbaum M . Multiple novel nonsynonymous CYP2B6 gene polymorphisms in Caucasians: demonstration of phenotypic null alleles. J Pharmacol Exp Ther. 2004; 311(1):34-43. DOI: 10.1124/jpet.104.068973. View

Solus J, Arietta B, Harris J, Sexton D, Steward J, McMunn C . Genetic variation in eleven phase I drug metabolism genes in an ethnically diverse population. Pharmacogenomics. 2004; 5(7):895-931. DOI: 10.1517/14622416.5.7.895. View

Milinkovic A, Martinez E . Nevirapine in the treatment of HIV. Expert Rev Anti Infect Ther. 2004; 2(3):367-73. DOI: 10.1586/14787210.2.3.367. View

Fortin C, Joly V . Efavirenz for HIV-1 infection in adults: an overview. Expert Rev Anti Infect Ther. 2004; 2(5):671-84. DOI: 10.1586/14789072.2.5.671. View

Haas D, Ribaudo H, Kim R, Tierney C, Wilkinson G, Gulick R . Pharmacogenetics of efavirenz and central nervous system side effects: an Adult AIDS Clinical Trials Group study. AIDS. 2004; 18(18):2391-400. View

10.

Hasse B, Gunthard H, Bleiber G, Krause M . Efavirenz intoxication due to slow hepatic metabolism. Clin Infect Dis. 2005; 40(3):e22-3. DOI: 10.1086/427031. View

11.

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(9):1358-61. DOI: 10.1086/429327. View

12.

Rotger M, Colombo S, Furrer H, Bleiber G, Buclin T, Lee B . Influence of CYP2B6 polymorphism on plasma and intracellular concentrations and toxicity of efavirenz and nevirapine in HIV-infected patients. Pharmacogenet Genomics. 2005; 15(1):1-5. DOI: 10.1097/01213011-200501000-00001. View

13.

Gutierrez F, Navarro A, Padilla S, Anton R, Masia M, Borras J . Prediction of neuropsychiatric adverse events associated with long-term efavirenz therapy, using plasma drug level monitoring. Clin Infect Dis. 2005; 41(11):1648-53. DOI: 10.1086/497835. View

14.

Klein K, Lang T, Saussele T, Barbosa-Sicard E, Schunck W, Eichelbaum M . 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(12):861-73. DOI: 10.1097/01213011-200512000-00004. View

15.

Ribaudo H, Haas D, Tierney C, Kim R, Wilkinson G, Gulick R . Pharmacogenetics of plasma efavirenz exposure after treatment discontinuation: an Adult AIDS Clinical Trials Group Study. Clin Infect Dis. 2006; 42(3):401-7. DOI: 10.1086/499364. View

16.

Wang J, Sonnerborg A, Rane A, Josephson F, Lundgren S, Stahle L . Identification of a novel specific CYP2B6 allele in Africans causing impaired metabolism of the HIV drug efavirenz. Pharmacogenet Genomics. 2006; 16(3):191-8. DOI: 10.1097/01.fpc.0000189797.03845.90. View

17.

Mehlotra R, Ziats M, Bockarie M, Zimmerman P . Prevalence of CYP2B6 alleles in malaria-endemic populations of West Africa and Papua New Guinea. Eur J Clin Pharmacol. 2006; 62(4):267-75. PMC: 4450653. DOI: 10.1007/s00228-005-0092-9. View

18.

Lang T, Klein K, Fischer J, Nussler A, Neuhaus P, Hofmann U . Extensive genetic polymorphism in the human CYP2B6 gene with impact on expression and function in human liver. Pharmacogenetics. 2001; 11(5):399-415. DOI: 10.1097/00008571-200107000-00004. View