CYP2B6 polymorphism and nonnucleoside reverse transcriptase inhibitor plasma concentrations in Chinese HIV-infected patients.
The purpose of this study was to investigate the frequency of CYP2B6 polymorphisms and their influence on plasma concentrations of efavirenz and nevirapine in HIV-infected Chinese patients. After written informed consent, 159 patients were enrolled at Shanghai Public Health Clinical Center. Genotyping for 516 G>T, 785 A>G, 983 T>C, and 1459 T>C polymorphisms in CYP2B6, together with CYP3A4 -392 A>G, CYP3A5 6986 A>G, and ABCB1 (2677 G>T/A, 3435 C>T), were performed. Plasma efavirenz and nevirapine concentrations of 120 patients at steady state were assessed by high-performance liquid chromatography-mass spectrometry. The minor allele frequency for CYP2B6 516 G>T, 785 A>G, 983 T>C, and 1459 T>C was 0.16, 0.24, 0, and 0, respectively; and 0.07, 0.32, 0.15, and 0.35 for CYP3A4 -392 A>G, CYP3A5 6986 A>G, ABCB1 2677 G>T/A, and ABCB1 3435 C>T, respectively. Univariate analysis indicated associations between 516 G>T (P < 0.01) with efavirenz but not nevirapine plasma concentrations. None of other genetic variants was associated with plasma efavirenz or nevirapine concentrations. Although CYP2B6 516 G>T was associated with high plasma efavirenz concentrations, such an association was not evident with nevirapine in this Chinese patient population. CYP3A4 -392 A>G, CYP3A5 6986 A>G, and ABCB1 (2677 G>T/A, 3435 C>T) had no significant impact on plasma efavirenz or nevirapine concentrations.
Chen
Jun
J
Department of Infectious Disease, Shanghai Public Health Clinical Center affiliated to Fudan University, Shanghai, China.
Sun
Jianjun
J
Ma
Qing
Q
Yao
Yaming
Y
Wang
Zhenyan
Z
Zhang
Lijun
L
Li
Li
L
Sun
Fuyan
F
Lu
Hongzhou
H
D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics; D000328:Adult; D000368:Aged; D000480:Alkynes; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics*; D044466:Asian People; D048588:Benzoxazines / Q000097:blood* / Q000493:pharmacokinetics / Q000627:therapeutic use; D002681:China; D002851:Chromatography, High Pressure Liquid; D003521:Cyclopropanes; D065702:Cytochrome P-450 CYP2B6; D051544:Cytochrome P-450 CYP3A / Q000235:genetics; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D015658:HIV Infections / Q000188:drug therapy* / Q000201:enzymology; D006801:Humans; D008297:Male; D013058:Mass Spectrometry; D008875:Middle Aged; D019829:Nevirapine / Q000097:blood* / Q000493:pharmacokinetics / Q000627:therapeutic use; D010089:Oxidoreductases, N-Demethylating / Q000235:genetics*; D011110:Polymorphism, Genetic; D018894:Reverse Transcriptase Inhibitors / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use
C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000480:Alkynes; D048588:Benzoxazines; D003521:Cyclopropanes; D018894:Reverse Transcriptase Inhibitors; 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; C098320:efavirenz