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Prevalence of Cytochrome P450 2B6 Single Nucleotide Polymorphism in an HIV-Positive Cohort in Jos, Nigeria: Implication for HIV Therapy

BACKGROUND: Africans exhibit great diversity in cytochrome P450 2B6 isoenzyme (CYP2B6), the major enzyme in efavirenz metabolism. AIM: We examined the frequency of two functional single nucleotide polymorphisms (SNPs) of the CYP2B6 pharmacogene in HIV-infected Nigerians on efavirenz-based antiretrov...

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Autores principales: Isaac, AO, Wetkos, DD, Oche, AO, Godwin, I, Phyllis, K, John, AC
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8576856/
https://www.ncbi.nlm.nih.gov/pubmed/33355828
http://dx.doi.org/10.4103/njcp.njcp_348_20
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author Isaac, AO
Wetkos, DD
Oche, AO
Godwin, I
Phyllis, K
John, AC
author_facet Isaac, AO
Wetkos, DD
Oche, AO
Godwin, I
Phyllis, K
John, AC
author_sort Isaac, AO
collection PubMed
description BACKGROUND: Africans exhibit great diversity in cytochrome P450 2B6 isoenzyme (CYP2B6), the major enzyme in efavirenz metabolism. AIM: We examined the frequency of two functional single nucleotide polymorphisms (SNPs) of the CYP2B6 pharmacogene in HIV-infected Nigerians on efavirenz-based antiretroviral therapy. The potential implications of the SNPs for HIV therapy were discussed. MATERIALS AND METHODS: A cross-sectional study conducted from July 2018 to December 2018 in a tertiary health facility in Nigeria. A random sample of a clinic cohort of HIV-infected adult Nigerians of different ethnicities was characterized for two key SNPs; CYP2B6:516G>, and CYP2B6:983T > C, defining the alleles CYP2B6*6 and CYP2B6*18, respectively. Hardy–Weinberg equilibrium was calculated to evaluate the genotype frequency distribution. RESULTS: Genotyping was successful for 262 (83%) of the 316 study participants. Of those with genotype results, mean age was 41 ± 8 years and 182 (69.5%) were female. The CYP2B6:516 G/G (extensive metabolizers), CYP2B6:516 G/T (intermediate metabolizers), and CYP2B6:516 T/T (poor metabolizers) genotype frequency was 35.9%, 46.6%, and 17.6%, respectively. Also, 88.9% and 11.1% of participants were carriers of the CYP2B6:983 T/T and CYP2B6:983 T/C (poor metabolizers) genotypes, respectively. There were no gender or age-related differences in the genotype distribution. The CYP2B6:516G >T allele frequencies showed no significant deviations from the Hardy-Weinberg equilibrium (P = 0.66). CONCLUSIONS: The intermediate metabolizer genotype was more common than the extensive and poor metabolizer genotypes in our study sample. We recommended further studies to investigate the risk of efavirenz underexposure and overexposure in carries of the extensive and poor metabolizer genotypes respectively in our patient population.
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spelling pubmed-85768562021-12-01 Prevalence of Cytochrome P450 2B6 Single Nucleotide Polymorphism in an HIV-Positive Cohort in Jos, Nigeria: Implication for HIV Therapy Isaac, AO Wetkos, DD Oche, AO Godwin, I Phyllis, K John, AC Niger J Clin Pract Article BACKGROUND: Africans exhibit great diversity in cytochrome P450 2B6 isoenzyme (CYP2B6), the major enzyme in efavirenz metabolism. AIM: We examined the frequency of two functional single nucleotide polymorphisms (SNPs) of the CYP2B6 pharmacogene in HIV-infected Nigerians on efavirenz-based antiretroviral therapy. The potential implications of the SNPs for HIV therapy were discussed. MATERIALS AND METHODS: A cross-sectional study conducted from July 2018 to December 2018 in a tertiary health facility in Nigeria. A random sample of a clinic cohort of HIV-infected adult Nigerians of different ethnicities was characterized for two key SNPs; CYP2B6:516G>, and CYP2B6:983T > C, defining the alleles CYP2B6*6 and CYP2B6*18, respectively. Hardy–Weinberg equilibrium was calculated to evaluate the genotype frequency distribution. RESULTS: Genotyping was successful for 262 (83%) of the 316 study participants. Of those with genotype results, mean age was 41 ± 8 years and 182 (69.5%) were female. The CYP2B6:516 G/G (extensive metabolizers), CYP2B6:516 G/T (intermediate metabolizers), and CYP2B6:516 T/T (poor metabolizers) genotype frequency was 35.9%, 46.6%, and 17.6%, respectively. Also, 88.9% and 11.1% of participants were carriers of the CYP2B6:983 T/T and CYP2B6:983 T/C (poor metabolizers) genotypes, respectively. There were no gender or age-related differences in the genotype distribution. The CYP2B6:516G >T allele frequencies showed no significant deviations from the Hardy-Weinberg equilibrium (P = 0.66). CONCLUSIONS: The intermediate metabolizer genotype was more common than the extensive and poor metabolizer genotypes in our study sample. We recommended further studies to investigate the risk of efavirenz underexposure and overexposure in carries of the extensive and poor metabolizer genotypes respectively in our patient population. 2020-12 /pmc/articles/PMC8576856/ /pubmed/33355828 http://dx.doi.org/10.4103/njcp.njcp_348_20 Text en https://creativecommons.org/licenses/by-nc-sa/4.0/This is an open access journal, and articles are distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 4.0 License, which allows others to remix, tweak, and build upon the work non-commercially, as long as appropriate credit is given and the new creations are licensed under the identical terms.
spellingShingle Article
Isaac, AO
Wetkos, DD
Oche, AO
Godwin, I
Phyllis, K
John, AC
Prevalence of Cytochrome P450 2B6 Single Nucleotide Polymorphism in an HIV-Positive Cohort in Jos, Nigeria: Implication for HIV Therapy
title Prevalence of Cytochrome P450 2B6 Single Nucleotide Polymorphism in an HIV-Positive Cohort in Jos, Nigeria: Implication for HIV Therapy
title_full Prevalence of Cytochrome P450 2B6 Single Nucleotide Polymorphism in an HIV-Positive Cohort in Jos, Nigeria: Implication for HIV Therapy
title_fullStr Prevalence of Cytochrome P450 2B6 Single Nucleotide Polymorphism in an HIV-Positive Cohort in Jos, Nigeria: Implication for HIV Therapy
title_full_unstemmed Prevalence of Cytochrome P450 2B6 Single Nucleotide Polymorphism in an HIV-Positive Cohort in Jos, Nigeria: Implication for HIV Therapy
title_short Prevalence of Cytochrome P450 2B6 Single Nucleotide Polymorphism in an HIV-Positive Cohort in Jos, Nigeria: Implication for HIV Therapy
title_sort prevalence of cytochrome p450 2b6 single nucleotide polymorphism in an hiv-positive cohort in jos, nigeria: implication for hiv therapy
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8576856/
https://www.ncbi.nlm.nih.gov/pubmed/33355828
http://dx.doi.org/10.4103/njcp.njcp_348_20
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