Drug transporter and metabolizing enzyme gene variants and nonnucleoside reverse-transcriptase inhibitor hepatotoxicity.
This nested case-control study examined relationships between MDR1, CYP2B6, and CYP3A4 variants and hepatotoxicity during antiretroviral therapy with either efavirenz- or nevirapine-containing regimens. Decreased risk of hepatotoxicity was associated with MDR1 3435C-->T (odds ratio, 0.254; P=.021). An interaction between MDR1 and hepatitis B surface antigen status predicted risk with 82% accuracy (P<.001).
Ritchie
Marylyn D
MD
Center for Human Genetics Research, Vanderbilt University School of Medicine, Nashville, TN 37232, USA. marylyn.ritchie@vanderbilt.edu
Haas
David W
DW
Motsinger
Alison A
AA
Donahue
John P
JP
Erdem
Huso
H
Raffanti
Stephen
S
Rebeiro
Peter
P
George
Alfred L
AL
Kim
Richard B
RB
Haines
Jonathan L
JL
Sterling
Timothy R
TR
D000328:Adult; D000480:Alkynes; D019380:Anti-HIV Agents / Q000009:adverse effects* / Q000378:metabolism / Q000627:therapeutic use; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics; D048588:Benzoxazines; D016022:Case-Control Studies; D056486:Chemical and Drug Induced Liver Injury; D003521:Cyclopropanes; D065702:Cytochrome P-450 CYP2B6; D051544:Cytochrome P-450 CYP3A; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics*; D005260:Female; D019450:Genes, MDR; D014644:Genetic Variation; D005838:Genotype; D015658:HIV Infections / Q000188:drug therapy; D015497:HIV-1; D006801:Humans; D008099:Liver / Q000187:drug effects; D008107:Liver Diseases / Q000235:genetics / Q000821:virology; D008297:Male; D019829:Nevirapine / Q000009:adverse effects* / Q000378:metabolism / Q000627:therapeutic use; D010078:Oxazines / Q000009:adverse effects* / Q000378:metabolism / Q000627:therapeutic use; D010089:Oxidoreductases, N-Demethylating / Q000235:genetics; D018894:Reverse Transcriptase Inhibitors / Q000009:adverse effects* / Q000378:metabolism / Q000627:therapeutic use
D000480:Alkynes; D019380:Anti-HIV Agents; D048588:Benzoxazines; D003521:Cyclopropanes; D010078:Oxazines; D018894:Reverse Transcriptase Inhibitors; D003577:Cytochrome P-450 Enzyme System; D019829:Nevirapine; D001189:Aryl Hydrocarbon Hydroxylases; C585599:CYP2B6 protein, human; D065702:Cytochrome P-450 CYP2B6; D051544:Cytochrome P-450 CYP3A; C510163:CYP3A4 protein, human; D010089:Oxidoreductases, N-Demethylating; C098320:efavirenz