1. Nevirapine-induced hepatotoxicity and pharmacogenetics: a retrospective study in a population from Mozambique.
- Author
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Ciccacci C, Borgiani P, Ceffa S, Sirianni E, Marazzi MC, Altan AM, Paturzo G, Bramanti P, Novelli G, and Palombi L
- Subjects
- ATP Binding Cassette Transporter, Subfamily B, ATP Binding Cassette Transporter, Subfamily B, Member 1 genetics, Alleles, Anti-HIV Agents therapeutic use, Aryl Hydrocarbon Hydroxylases genetics, Case-Control Studies, Chemical and Drug Induced Liver Injury etiology, Cytochrome P-450 CYP2B6, Cytochrome P-450 CYP3A genetics, Female, Genetic Association Studies, Genotype, HIV Infections genetics, Haplotypes, Humans, Infectious Disease Transmission, Vertical prevention & control, Male, Mozambique, Nevirapine therapeutic use, Odds Ratio, Oxidoreductases, N-Demethylating genetics, Polymorphism, Single Nucleotide genetics, Pregnancy, Retrospective Studies, Anti-HIV Agents adverse effects, Chemical and Drug Induced Liver Injury genetics, HIV Infections drug therapy, Nevirapine adverse effects
- 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.
- Published
- 2010
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