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.

Ciccacci, C., Di Fusco, D., Marazzi, M., Zimba, I., Erba, F., Novelli, G., et al. (2013). Association between CYP2B6 polymorphisms and Nevirapine-induced SJS/TEN: a pharmacogenetics study. EUROPEAN JOURNAL OF CLINICAL PHARMACOLOGY [10.1007/s00228-013-1549-x].

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

ERBA, FULVIO;NOVELLI, GIUSEPPE;PALOMBI, LEONARDO;BORGIANI, PAOLA;LIOTTA, GIUSEPPE
2013

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.
Pubblicato
Rilevanza internazionale
Articolo
Esperti anonimi
Settore MED/42 - Igiene Generale e Applicata
Settore MED/03 - Genetica Medica
English
Con Impact Factor ISI
Steven-Jhonson Syndrome, HIV/AIDS, Pharmacogenomics, Nevirapine
Ciccacci, C., Di Fusco, D., Marazzi, M., Zimba, I., Erba, F., Novelli, G., et al. (2013). Association between CYP2B6 polymorphisms and Nevirapine-induced SJS/TEN: a pharmacogenetics study. EUROPEAN JOURNAL OF CLINICAL PHARMACOLOGY [10.1007/s00228-013-1549-x].
Ciccacci, C; Di Fusco, D; Marazzi, M; Zimba, I; Erba, F; Novelli, G; Palombi, L; Borgiani, P; Liotta, G
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2108/79300
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