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

Pharmacogenomics. 2010 Jan;11(1):23-31. doi: 10.2217/pgs.09.142.

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.

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B
  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / genetics
  • Alleles
  • Anti-HIV Agents / adverse effects*
  • Anti-HIV Agents / therapeutic use
  • Aryl Hydrocarbon Hydroxylases / genetics
  • Case-Control Studies
  • Chemical and Drug Induced Liver Injury / etiology
  • Chemical and Drug Induced Liver Injury / genetics*
  • Cytochrome P-450 CYP2B6
  • Cytochrome P-450 CYP3A / genetics
  • Female
  • Genetic Association Studies
  • Genotype
  • HIV Infections / drug therapy*
  • HIV Infections / genetics
  • Haplotypes
  • Humans
  • Infectious Disease Transmission, Vertical / prevention & control
  • Male
  • Mozambique
  • Nevirapine / adverse effects*
  • Nevirapine / therapeutic use
  • Odds Ratio
  • Oxidoreductases, N-Demethylating / genetics
  • Polymorphism, Single Nucleotide / genetics
  • Pregnancy
  • Retrospective Studies

Substances

  • ABCB1 protein, human
  • ATP Binding Cassette Transporter, Subfamily B
  • ATP Binding Cassette Transporter, Subfamily B, Member 1
  • Anti-HIV Agents
  • Nevirapine
  • Aryl Hydrocarbon Hydroxylases
  • CYP2B6 protein, human
  • CYP3A5 protein, human
  • Cytochrome P-450 CYP2B6
  • Cytochrome P-450 CYP3A
  • CYP3A4 protein, human
  • Oxidoreductases, N-Demethylating