title: Distribution of allelic and genotypic frequencies of NAT2 and CYP2E1 variants in Moroccan population.
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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Centre de génomique humaine, Faculté de médecine et de pharmacie, Université Mohammed V, Rabat, Morocco. soukainaguaoua@gmail.com.
authors.forename: Soukaina
authors.initials: S
authors.lastname: Guaoua
authors.affiliation: Centre de génomique humaine, Faculté de médecine et de pharmacie, Université Mohammed V, Rabat, Morocco. i.ratbi@um5s.net.ma.
authors.forename: Ilham
authors.initials: I
authors.lastname: Ratbi
authors.affiliation: Département de génétique médicale, Institut National d'Hygiène, Rabat, Morocco. fz_laarabi@yahoo.fr.
authors.forename: Fatima Zahra
authors.initials: FZ
authors.lastname: Laarabi
authors.affiliation: Centre de génomique humaine, Faculté de médecine et de pharmacie, Université Mohammed V, Rabat, Morocco. sihamgen@yahoo.fr.|Département de génétique médicale, Institut National d'Hygiène, Rabat, Morocco. sihamgen@yahoo.fr.
authors.forename: Siham Chafai
authors.initials: SC
authors.lastname: Elalaoui
authors.affiliation: Centre de génomique humaine, Faculté de médecine et de pharmacie, Université Mohammed V, Rabat, Morocco. imane_cj@yahoo.fr.|Département de génétique médicale, Institut National d'Hygiène, Rabat, Morocco. imane_cj@yahoo.fr.
authors.forename: Imane Cherkaoui
authors.initials: IC
authors.lastname: Jaouad
authors.affiliation: Centre National de Référence en Néonatologie et en Nutrition, Rabat, Morocco. barakatamina@hotmail.fr.
authors.forename: Amina
authors.initials: A
authors.lastname: Barkat
authors.affiliation: Centre de génomique humaine, Faculté de médecine et de pharmacie, Université Mohammed V, Rabat, Morocco. sefianigen@hotmail.com.|Département de génétique médicale, Institut National d'Hygiène, Rabat, Morocco. sefianigen@hotmail.com.
authors.forename: Abdelaziz
authors.initials: A
authors.lastname: Sefiani
mesh_terms: D000995:Antitubercular Agents / Q000009:adverse effects; D001191:Arylamine N-Acetyltransferase / Q000235:genetics*; D056486:Chemical and Drug Induced Liver Injury / Q000453:epidemiology / Q000235:genetics*; D019392:Cytochrome P-450 CYP2E1 / Q000235:genetics*; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006801:Humans; D007231:Infant, Newborn; D007538:Isoniazid / Q000009:adverse effects; D009018:Morocco / Q000453:epidemiology; D020641:Polymorphism, Single Nucleotide; D015995:Prevalence; D012307:Risk Factors
chemical_list: D000995:Antitubercular Agents; D019392:Cytochrome P-450 CYP2E1; D001191:Arylamine N-Acetyltransferase; C478900:NAT2 protein, human; D007538:Isoniazid