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 language | English |
|---|---|
| Pages (from-to) | 1909-1916 |
| Number of pages | 8 |
| Journal | European Journal of Clinical Pharmacology |
| Volume | 69 |
| Issue number | 11 |
| DOIs | |
| Publication status | Published - 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
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 journal › Article
}
TY - JOUR
T1 - Association between CYP2B6 polymorphisms and Nevirapine-induced SJS/TEN
T2 - A pharmacogenetics study
AU - Ciccacci, Cinzia
AU - Di Fusco, Davide
AU - Marazzi, Maria C.
AU - Zimba, Ines
AU - Erba, Fulvio
AU - Novelli, Giuseppe
AU - Palombi, Leonardo
AU - Borgiani, Paola
AU - Liotta, Giuseppe
PY - 2013/11
Y1 - 2013/11
N2 - 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.
AB - 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.
KW - CYP2B6 gene
KW - Nevirapine
KW - Pharmacogenomics
KW - Single nucleotide polymorphisms
KW - Stevens-Johnson syndrome
KW - Toxic epidermal necrolysis
UR - http://www.scopus.com/inward/record.url?scp=84886774838&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84886774838&partnerID=8YFLogxK
U2 - 10.1007/s00228-013-1549-x
DO - 10.1007/s00228-013-1549-x
M3 - Article
C2 - 23774940
AN - SCOPUS:84886774838
VL - 69
SP - 1909
EP - 1916
JO - European Journal of Clinical Pharmacology
JF - European Journal of Clinical Pharmacology
SN - 0031-6970
IS - 11
ER -