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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.

Distribution of allelic and genotypic frequencies of NAT2 and CYP2E1variants in Moroccan population