Human cytochrome P450 2B6 genetic variability in Botswana: a case of haplotype diversity and convergent phenotypes

Abstract Identification of inter-individual variability for drug metabolism through cytochrome P450 2B6 (CYP2B6) enzyme is important for understanding the differences in clinical responses to malaria and HIV. This study evaluates the distribution of CYP2B6 alleles, haplotypes and inferred metabolic...

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Autores principales:	Leabaneng Tawe, Thato Motshoge, Pleasure Ramatlho, Naledi Mutukwa, Charles Waithaka Muthoga, Ghyslaine Bruna Djeunang Dongho, Axel Martinelli, Elias Peloewetse, Gianluca Russo, Isaac Kweku Quaye, Giacomo Maria Paganotti
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2018
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/11b544b28c044d92bf3551d5f6492f3e
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spelling	oai:doaj.org-article:11b544b28c044d92bf3551d5f6492f3e2021-12-02T15:07:43ZHuman cytochrome P450 2B6 genetic variability in Botswana: a case of haplotype diversity and convergent phenotypes10.1038/s41598-018-23350-12045-2322https://doaj.org/article/11b544b28c044d92bf3551d5f6492f3e2018-03-01T00:00:00Zhttps://doi.org/10.1038/s41598-018-23350-1https://doaj.org/toc/2045-2322Abstract Identification of inter-individual variability for drug metabolism through cytochrome P450 2B6 (CYP2B6) enzyme is important for understanding the differences in clinical responses to malaria and HIV. This study evaluates the distribution of CYP2B6 alleles, haplotypes and inferred metabolic phenotypes among subjects with different ethnicity in Botswana. A total of 570 subjects were analyzed for CYP2B6 polymorphisms at position 516 G > T (rs3745274), 785 A > G (rs2279343) and 983 T > C (rs28399499). Samples were collected in three districts of Botswana where the population belongs to Bantu (Serowe/Palapye and Chobe) and San-related (Ghanzi) ethnicity. The three districts showed different haplotype composition according to the ethnic background but similar metabolic inferred phenotypes, with 59.12%, 34.56%, 2.10% and 4.21% of the subjects having, respectively, an extensive, intermediate, slow and rapid metabolic profile. The results hint at the possibility of a convergent adaptation of detoxifying metabolic phenotypes despite a different haplotype structure due to the different genetic background. The main implication is that, while there is substantial homogeneity of metabolic inferred phenotypes among the country, the response to drugs metabolized via CYP2B6 could be individually associated to an increased risk of treatment failure and toxicity. These are important facts since Botswana is facing malaria elimination and a very high HIV prevalence.Leabaneng TaweThato MotshogePleasure RamatlhoNaledi MutukwaCharles Waithaka MuthogaGhyslaine Bruna Djeunang DonghoAxel MartinelliElias PeloewetseGianluca RussoIsaac Kweku QuayeGiacomo Maria PaganottiNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 8, Iss 1, Pp 1-9 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Leabaneng Tawe Thato Motshoge Pleasure Ramatlho Naledi Mutukwa Charles Waithaka Muthoga Ghyslaine Bruna Djeunang Dongho Axel Martinelli Elias Peloewetse Gianluca Russo Isaac Kweku Quaye Giacomo Maria Paganotti Human cytochrome P450 2B6 genetic variability in Botswana: a case of haplotype diversity and convergent phenotypes
description	Abstract Identification of inter-individual variability for drug metabolism through cytochrome P450 2B6 (CYP2B6) enzyme is important for understanding the differences in clinical responses to malaria and HIV. This study evaluates the distribution of CYP2B6 alleles, haplotypes and inferred metabolic phenotypes among subjects with different ethnicity in Botswana. A total of 570 subjects were analyzed for CYP2B6 polymorphisms at position 516 G > T (rs3745274), 785 A > G (rs2279343) and 983 T > C (rs28399499). Samples were collected in three districts of Botswana where the population belongs to Bantu (Serowe/Palapye and Chobe) and San-related (Ghanzi) ethnicity. The three districts showed different haplotype composition according to the ethnic background but similar metabolic inferred phenotypes, with 59.12%, 34.56%, 2.10% and 4.21% of the subjects having, respectively, an extensive, intermediate, slow and rapid metabolic profile. The results hint at the possibility of a convergent adaptation of detoxifying metabolic phenotypes despite a different haplotype structure due to the different genetic background. The main implication is that, while there is substantial homogeneity of metabolic inferred phenotypes among the country, the response to drugs metabolized via CYP2B6 could be individually associated to an increased risk of treatment failure and toxicity. These are important facts since Botswana is facing malaria elimination and a very high HIV prevalence.
format	article
author	Leabaneng Tawe Thato Motshoge Pleasure Ramatlho Naledi Mutukwa Charles Waithaka Muthoga Ghyslaine Bruna Djeunang Dongho Axel Martinelli Elias Peloewetse Gianluca Russo Isaac Kweku Quaye Giacomo Maria Paganotti
author_facet	Leabaneng Tawe Thato Motshoge Pleasure Ramatlho Naledi Mutukwa Charles Waithaka Muthoga Ghyslaine Bruna Djeunang Dongho Axel Martinelli Elias Peloewetse Gianluca Russo Isaac Kweku Quaye Giacomo Maria Paganotti
author_sort	Leabaneng Tawe
title	Human cytochrome P450 2B6 genetic variability in Botswana: a case of haplotype diversity and convergent phenotypes
title_short	Human cytochrome P450 2B6 genetic variability in Botswana: a case of haplotype diversity and convergent phenotypes
title_full	Human cytochrome P450 2B6 genetic variability in Botswana: a case of haplotype diversity and convergent phenotypes
title_fullStr	Human cytochrome P450 2B6 genetic variability in Botswana: a case of haplotype diversity and convergent phenotypes
title_full_unstemmed	Human cytochrome P450 2B6 genetic variability in Botswana: a case of haplotype diversity and convergent phenotypes
title_sort	human cytochrome p450 2b6 genetic variability in botswana: a case of haplotype diversity and convergent phenotypes
publisher	Nature Portfolio
publishDate	2018
url	https://doaj.org/article/11b544b28c044d92bf3551d5f6492f3e
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Human cytochrome P450 2B6 genetic variability in Botswana: a case of haplotype diversity and convergent phenotypes

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