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


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).


CONCLUSIONS
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.
Ciccacci
Cinzia
C
Department of Biopathology & Diagnostic Imaging, Section of Genetics, Tor Vergata University, Rome, Italy.
Borgiani
Paola
P
Ceffa
Susanna
S
Sirianni
Elisabetta
E
Marazzi
Maria C
MC
Altan
Anna M Doro
AM
Paturzo
Giovanna
G
Bramanti
Placido
P
Novelli
Giuseppe
G
Palombi
Leonardo
L
D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics; D000483:Alleles; D019380:Anti-HIV Agents / Q000009:adverse effects* / Q000627:therapeutic use; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics; D016022:Case-Control Studies; D056486:Chemical and Drug Induced Liver Injury / Q000209:etiology / Q000235:genetics*; D065702:Cytochrome P-450 CYP2B6; D051544:Cytochrome P-450 CYP3A / Q000235:genetics; D005260:Female; D056726:Genetic Association Studies; D005838:Genotype; D015658:HIV Infections / Q000188:drug therapy* / Q000235:genetics; D006239:Haplotypes; D006801:Humans; D018445:Infectious Disease Transmission, Vertical / Q000517:prevention & control; D008297:Male; D009073:Mozambique; D019829:Nevirapine / Q000009:adverse effects* / Q000627:therapeutic use; D016017:Odds Ratio; D010089:Oxidoreductases, N-Demethylating / Q000235:genetics; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D011247:Pregnancy; D012189:Retrospective Studies
C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D019380:Anti-HIV Agents; D019829:Nevirapine; D001189:Aryl Hydrocarbon Hydroxylases; C585599:CYP2B6 protein, human; C510164:CYP3A5 protein, human; D065702:Cytochrome P-450 CYP2B6; D051544:Cytochrome P-450 CYP3A; C510163:CYP3A4 protein, human; D010089:Oxidoreductases, N-Demethylating