Distribution of allelic and genotypic frequencies of NAT2 and CYP2E1 variants in Moroccan population.
BMC Genet
; 15: 156, 2014 Dec 29.
Article
en En
| MEDLINE
| ID: mdl-25544508
ABSTRACT
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.
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Arilamina N-Acetiltransferasa
/
Citocromo P-450 CYP2E1
/
Enfermedad Hepática Inducida por Sustancias y Drogas
Tipo de estudio:
Etiology_studies
/
Prevalence_studies
/
Prognostic_studies
/
Risk_factors_studies
Límite:
Humans
/
Newborn
País/Región como asunto:
Africa
Idioma:
En
Revista:
BMC Genet
Asunto de la revista:
BIOLOGIA MOLECULAR
/
BIOTECNOLOGIA
Año:
2014
Tipo del documento:
Article
País de afiliación:
Marruecos