Pharmacogenetics of nevirapine-associated hepatotoxicity: an Adult AIDS Clinical Trials Group collaboration.
Associations have been reported between an MDR1 variant and responses to nonnucleoside reverse-transcriptase inhibitors. We explored associations between MDR1, CYP2B6, and CYP3A polymorphisms and nevirapine hepatotoxicity. Among participants in a randomized study in South Africa (FTC-302), MDR1 3435C-->T was significantly associated with decreased risk of hepatotoxicity (risk ratio, 0.30; P=.016).
Haas
David W
DW
Microbiology and Immunology, Center for Human Genetics Research, Vanderbilt University School of Medicine, Nashville, Tennessee 37203, USA. david.w.haas@vanderbilt.edu
Bartlett
John A
JA
Andersen
Janet W
JW
Sanne
Ian
I
Wilkinson
Grant R
GR
Hinkle
John
J
Rousseau
Franck
F
Ingram
Christiana D
CD
Shaw
Audrey
A
Lederman
Michael M
MM
Kim
Richard B
RB
D000328:Adult; D019380:Anti-HIV Agents / Q000009:adverse effects* / Q000378:metabolism / Q000627:therapeutic use; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics; D016022:Case-Control Studies; D056486:Chemical and Drug Induced Liver Injury; D065702:Cytochrome P-450 CYP2B6; D051544:Cytochrome P-450 CYP3A; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D019450:Genes, MDR; 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; D010089:Oxidoreductases, N-Demethylating / Q000235:genetics; D011110:Polymorphism, Genetic; D016032:Randomized Controlled Trials as Topic; D018894:Reverse Transcriptase Inhibitors / Q000009:adverse effects* / Q000378:metabolism / Q000627:therapeutic use; D013019:South Africa
D019380:Anti-HIV Agents; 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