Association between CYP2B6 polymorphisms and Nevirapine-induced SJS/TEN: A pharmacogenetics study

Cinzia Ciccacci, Davide Di Fusco, Maria C. Marazzi, Ines Zimba, Fulvio Erba, Giuseppe Novelli, Leonardo Palombi, Paola Borgiani, Giuseppe Liotta

Research output: Contribution to journalArticle

Abstract

Purpose: 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.

Original languageEnglish
Pages (from-to)1909-1916
Number of pages8
JournalEuropean Journal of Clinical Pharmacology
Volume69
Issue number11
DOIs
Publication statusPublished - Nov 2013

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Keywords

  • CYP2B6 gene
  • Nevirapine
  • Pharmacogenomics
  • Single nucleotide polymorphisms
  • Stevens-Johnson syndrome
  • Toxic epidermal necrolysis

ASJC Scopus subject areas

  • Pharmacology (medical)
  • Pharmacology

Cite this

Ciccacci, C., Di Fusco, D., Marazzi, M. C., Zimba, I., Erba, F., Novelli, G., Palombi, L., Borgiani, P., & Liotta, G. (2013). Association between CYP2B6 polymorphisms and Nevirapine-induced SJS/TEN: A pharmacogenetics study. European Journal of Clinical Pharmacology, 69(11), 1909-1916. https://doi.org/10.1007/s00228-013-1549-x