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

Fingerprint

Nevirapine
Stevens-Johnson Syndrome
Cytochrome P-450 CYP3A
Cytochromes
Single Nucleotide Polymorphism
Odds Ratio
Mozambique
Genes
Reverse Transcriptase Inhibitors
Virus Diseases
Haplotypes
Cytochrome P-450 CYP2B6
Pharmacogenomic Testing
Alleles
Genotype
Phenotype
Skin
Enzymes

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., ... 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

Association between CYP2B6 polymorphisms and Nevirapine-induced SJS/TEN : A pharmacogenetics study. / Ciccacci, Cinzia; Di Fusco, Davide; Marazzi, Maria C.; Zimba, Ines; Erba, Fulvio; Novelli, Giuseppe; Palombi, Leonardo; Borgiani, Paola; Liotta, Giuseppe.

In: European Journal of Clinical Pharmacology, Vol. 69, No. 11, 11.2013, p. 1909-1916.

Research output: Contribution to journalArticle

Ciccacci, C, Di Fusco, D, Marazzi, MC, 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, vol. 69, no. 11, pp. 1909-1916. https://doi.org/10.1007/s00228-013-1549-x
Ciccacci, Cinzia ; Di Fusco, Davide ; Marazzi, Maria C. ; Zimba, Ines ; Erba, Fulvio ; Novelli, Giuseppe ; Palombi, Leonardo ; Borgiani, Paola ; Liotta, Giuseppe. / Association between CYP2B6 polymorphisms and Nevirapine-induced SJS/TEN : A pharmacogenetics study. In: European Journal of Clinical Pharmacology. 2013 ; Vol. 69, No. 11. pp. 1909-1916.
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