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

作者：Ciccacci Cinzia; Borgiani Paola^*; Ceffa Susanna; Sirianni Elisabetta; Marazzi Maria C; Altan Anna M Doro; Paturzo Giovanna; Bramanti Placido; Novelli Giuseppe; Palombi Leonardo

来源：Pharmacogenomics, 2010, 11(1): 23-31.

DOI：10.2217/PGS.09.142

• ABCB1
• adverse reactions
• CYP2B6
• CYP3A4
• CYP3A5 hepatotoxicity
• nevirapine
• NVP
• pharmacogenetics
• pharmacogenomics
• SNP

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.

• 出版日期2010-1