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Distribution of allelic and genotypic frequencies of NAT2 and CYP2E1 variants in Moroccan population
BACKGROUND: Several pathogenesis and genetic factors influence predisposition to antituberculosis drug-induced hepatotoxicity (ATDH) especially for isoniazid (INH). However, the major susceptibility genes for ATDH are N-acetyltransferase 2 (NAT2) and cytochrome P450 2E1 (CYP2E1). NAT2 gene determine...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4299568/ https://www.ncbi.nlm.nih.gov/pubmed/25544508 http://dx.doi.org/10.1186/s12863-014-0156-x |
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author | Guaoua, Soukaina Ratbi, Ilham Laarabi, Fatima Zahra Elalaoui, Siham Chafai Jaouad, Imane Cherkaoui Barkat, Amina Sefiani, Abdelaziz |
author_facet | Guaoua, Soukaina Ratbi, Ilham Laarabi, Fatima Zahra Elalaoui, Siham Chafai Jaouad, Imane Cherkaoui Barkat, Amina Sefiani, Abdelaziz |
author_sort | Guaoua, Soukaina |
collection | PubMed |
description | BACKGROUND: Several pathogenesis and genetic factors influence predisposition to antituberculosis drug-induced hepatotoxicity (ATDH) especially for isoniazid (INH). However, the major susceptibility genes for ATDH are N-acetyltransferase 2 (NAT2) and cytochrome P450 2E1 (CYP2E1). NAT2 gene determines the individual’s acetylator status (fast, intermediate or slow) to metabolize drugs and xenobiotics, while CYP2E1 c1/c1 genotype carriers had an increased risk of ATDH. Polymorphisms of the NAT2 and CYP2E1 genes vary remarkably among the populations of different ethnic origins. The aim of this study was to determine, for the first time, the frequency of slow acetylators in Moroccan population by genotyping of NAT2 gene variants and determining the genotype c1/c1 for CYP2E1 gene, in order to predict adverse effects of Tuberculosis treatment, particularly hepatotoxicity. RESULTS: The frequencies of specific NAT2 alleles were 53%, 25%, 2% and 4% for NAT2*5, NAT2*6, NAT2*7 and NAT2*14 respectively among 163 Moroccan studied group. Genotyping of CYP2E1 gene, by real-time polymerase chain reaction using TaqMan probes, revealed frequencies of 98.5% for c1/c1 and 1.5% for c1/c2 among 130 Moroccan studied group. CONCLUSION: The most prevalent genotypes of NAT2 gene in Moroccans are those which encode slow acetylation phenotype (72.39%), leading to a high risk of ATDH. Most Moroccans are homozygous for c1 allele of CYP2E1 gene which aggravates hepatotoxicity in slow acetylators. This genetic background should be taken into account in determining the minimum dose of INH needed to treat Moroccan TB patients, in order to decrease adverse effects. |
format | Online Article Text |
id | pubmed-4299568 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-42995682015-01-21 Distribution of allelic and genotypic frequencies of NAT2 and CYP2E1 variants in Moroccan population Guaoua, Soukaina Ratbi, Ilham Laarabi, Fatima Zahra Elalaoui, Siham Chafai Jaouad, Imane Cherkaoui Barkat, Amina Sefiani, Abdelaziz BMC Genet Research Article BACKGROUND: Several pathogenesis and genetic factors influence predisposition to antituberculosis drug-induced hepatotoxicity (ATDH) especially for isoniazid (INH). However, the major susceptibility genes for ATDH are N-acetyltransferase 2 (NAT2) and cytochrome P450 2E1 (CYP2E1). NAT2 gene determines the individual’s acetylator status (fast, intermediate or slow) to metabolize drugs and xenobiotics, while CYP2E1 c1/c1 genotype carriers had an increased risk of ATDH. Polymorphisms of the NAT2 and CYP2E1 genes vary remarkably among the populations of different ethnic origins. The aim of this study was to determine, for the first time, the frequency of slow acetylators in Moroccan population by genotyping of NAT2 gene variants and determining the genotype c1/c1 for CYP2E1 gene, in order to predict adverse effects of Tuberculosis treatment, particularly hepatotoxicity. RESULTS: The frequencies of specific NAT2 alleles were 53%, 25%, 2% and 4% for NAT2*5, NAT2*6, NAT2*7 and NAT2*14 respectively among 163 Moroccan studied group. Genotyping of CYP2E1 gene, by real-time polymerase chain reaction using TaqMan probes, revealed frequencies of 98.5% for c1/c1 and 1.5% for c1/c2 among 130 Moroccan studied group. CONCLUSION: The most prevalent genotypes of NAT2 gene in Moroccans are those which encode slow acetylation phenotype (72.39%), leading to a high risk of ATDH. Most Moroccans are homozygous for c1 allele of CYP2E1 gene which aggravates hepatotoxicity in slow acetylators. This genetic background should be taken into account in determining the minimum dose of INH needed to treat Moroccan TB patients, in order to decrease adverse effects. BioMed Central 2014-12-29 /pmc/articles/PMC4299568/ /pubmed/25544508 http://dx.doi.org/10.1186/s12863-014-0156-x Text en © Guaoua et al.; licensee Biomed Central. 2014 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. |
spellingShingle | Research Article Guaoua, Soukaina Ratbi, Ilham Laarabi, Fatima Zahra Elalaoui, Siham Chafai Jaouad, Imane Cherkaoui Barkat, Amina Sefiani, Abdelaziz Distribution of allelic and genotypic frequencies of NAT2 and CYP2E1 variants in Moroccan population |
title | Distribution of allelic and genotypic frequencies of NAT2 and CYP2E1 variants in Moroccan population |
title_full | Distribution of allelic and genotypic frequencies of NAT2 and CYP2E1 variants in Moroccan population |
title_fullStr | Distribution of allelic and genotypic frequencies of NAT2 and CYP2E1 variants in Moroccan population |
title_full_unstemmed | Distribution of allelic and genotypic frequencies of NAT2 and CYP2E1 variants in Moroccan population |
title_short | Distribution of allelic and genotypic frequencies of NAT2 and CYP2E1 variants in Moroccan population |
title_sort | distribution of allelic and genotypic frequencies of nat2 and cyp2e1 variants in moroccan population |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4299568/ https://www.ncbi.nlm.nih.gov/pubmed/25544508 http://dx.doi.org/10.1186/s12863-014-0156-x |
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