title: Association between CYP2B6 polymorphisms and Nevirapine-induced SJS/TEN: a pharmacogenetics study.
abstract: OBJECTIVE
  Nevirapine (NVP) is a non-nucleoside reverse transcriptase inhibitor, widely prescribed for type 1 human immunodeficiency virus infection. A small proportion of individuals treated with NVP experience severe cutaneous adverse events, including Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). Our aim was to verify whether genetic variability in NVP-metabolizing cytochromes or in transporter genes could be involved in susceptibility to SJS/TEN.
  
  
  METHODS
  Twenty-seven patients with NVP-induced SJS/TEN and 78 controls, all from Mozambique, were genotyped for the ABCB1 and ABCC10 transporter genes and for CYP2B6, CYP3A4 and CYP3A5 cytochrome gene variants. A case-control and a genotype-phenotype analysis were performed.
  
  
  RESULTS
  CYP2B6 G516T and T983C single nucleotide polymorphisms (SNPs) were found to be associated with SJS/TEN susceptibility. The 983C allele in particular was found to be highly associated with a higher risk to develop SJS/TEN [odds ratio (OR) 4.2, P = 0.0047]. The GT haplotype (wildtype for both SNPs) showed a protective effect, with an OR = 0.33 (P = 0.0016).
  
  
  CONCLUSIONS
  This is the first study showing that genetic variability in a metabolizing enzyme can also contribute to NVP-induced SJS/TEN susceptibility.
authors.affiliation: Department of Biomedicine and Prevention, Genetics Section, School of Medicine, University of Rome "Tor Vergata", 00133, Rome, Italy.
authors.forename: Cinzia
authors.initials: C
authors.lastname: Ciccacci
authors.forename: Davide
authors.initials: D
authors.lastname: Di Fusco
authors.forename: Maria C
authors.initials: MC
authors.lastname: Marazzi
authors.forename: Ines
authors.initials: I
authors.lastname: Zimba
authors.forename: Fulvio
authors.initials: F
authors.lastname: Erba
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Novelli
authors.forename: Leonardo
authors.initials: L
authors.lastname: Palombi
authors.forename: Paola
authors.initials: P
authors.lastname: Borgiani
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Liotta
mesh_terms: D000328:Adult; D019380:Anti-HIV Agents / Q000009:adverse effects*; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics*; D065702:Cytochrome P-450 CYP2B6; D005260:Female; D005838:Genotype; D015658:HIV Infections / Q000188:drug therapy / Q000235:genetics; D006801:Humans; D019829:Nevirapine / Q000009:adverse effects*; D020641:Polymorphism, Single Nucleotide; D013262:Stevens-Johnson Syndrome / Q000209:etiology / Q000235:genetics*
chemical_list: D019380:Anti-HIV Agents; D019829:Nevirapine; D001189:Aryl Hydrocarbon Hydroxylases; C585599:CYP2B6 protein, human; D065702:Cytochrome P-450 CYP2B6