Nevirapine-induced hepatotoxicity and pharmacogenetics: A retrospective study in a population from Mozambique

Cinzia Ciccacci, Paola Borgiani, Susanna Ceffa, Elisabetta Sirianni, Maria C. Marazzi, Anna M. Doro Altan, Giovanna Paturzo, Placido Bramanti, Giuseppe Novelli, Leonardo Palombi

Research output: Contribution to journalArticle

Abstract

Aims: Nevirapine is widely used to treat HIV-1 infection to prevent mother-to-child transmission; unfortunately adverse drug reactions have been reported. Our aim was to identify genes/variants involved in nevirapine-induced hepatotoxicity. Materials & methods: Patients from Mozambique, 78 with nevirapine-induced hepatotoxicity and 78 without adverse events, were genotyped for ABCB1, CYP2B6, CYP3A4 and CYP3A5 gene variants. We conducted a case-control association study and a genotype/phenotype correlation analysis. Results: The ABCB1 c.3435C>T SNP was associated with hepatotoxicity (p = 0.038), with the variant T allele showing a protective effect (odds ratio: 0.42). Moreover, four SNPs in the CYP2B6 and CYP3A5 genes resulted significantly correlated with transaminase values. In particular, for the CYP2B6 c.983T>C SNP, the difference in the alanine aminotransferase mean values were highly significant between TT and TC genotypes (p <0.001). Conclusion: Our preliminary results confirm the contribution of the ABCB1 c.3435C>T SNP in nevirapine-induced hepatotoxicity risk and, at the same time, suggest the necessity for further studies.

Original languageEnglish
Pages (from-to)23-31
Number of pages9
JournalPharmacogenomics
Volume11
Issue number1
DOIs
Publication statusPublished - 2010

Keywords

  • ABCB1
  • Adverse reactions
  • CYP2B6
  • CYP3A4
  • CYP3A5
  • Hepatotoxicity
  • Nevirapine
  • NVP
  • Pharmacogenetics
  • Pharmacogenomics
  • SNP

ASJC Scopus subject areas

  • Pharmacology
  • Genetics
  • Molecular Medicine

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    Ciccacci, C., Borgiani, P., Ceffa, S., Sirianni, E., Marazzi, M. C., Doro Altan, A. M., Paturzo, G., Bramanti, P., Novelli, G., & Palombi, L. (2010). Nevirapine-induced hepatotoxicity and pharmacogenetics: A retrospective study in a population from Mozambique. Pharmacogenomics, 11(1), 23-31. https://doi.org/10.2217/pgs.09.142