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European Journal of Clinical Pharmacology

, Volume 69, Issue 11, pp 1909–1916 | Cite as

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
Pharmacogenetics

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.

Keywords

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

Notes

Competing interests

None.

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Copyright information

© Springer-Verlag Berlin Heidelberg 2013

Authors and Affiliations

  • Cinzia Ciccacci
    • 1
  • Davide Di Fusco
    • 1
  • Maria C. Marazzi
    • 2
  • Ines Zimba
    • 3
  • Fulvio Erba
    • 4
  • Giuseppe Novelli
    • 1
  • Leonardo Palombi
    • 4
  • Paola Borgiani
    • 1
  • Giuseppe Liotta
    • 4
  1. 1.Department of Biomedicine and Prevention, Genetics Section, School of MedicineUniversity of Rome “Tor Vergata”RomeItaly
  2. 2.LUMSA UniversityRomeItaly
  3. 3.DREAM ProgramMaputoMozambique
  4. 4.Department of Biomedicine and Prevention, Epidemiology SectionUniversity of Rome “Tor Vergata”RomeItaly

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