CYP2B6 516G>T (rs3745274) and smoking status are associated with efavirenz plasma concentration in a Serbian cohort of HIV patients.
BACKGROUND
Genetic factors have been associated with efavirenz (EFV) plasma concentrations in different populations. In this study, we investigated the effects of CYP2B6 516G>T (rs3745274), CYP2B6 c.485-18C>T (rs4803419), CAR c.540C>T (rs2307424), CAR c.152-1089T>C (rs3003596), and smoking status in a cohort of Serbian patients with HIV.


METHODS
Patients with HIV positive, all whites, were recruited from the HIV/AIDS Center at the Infectious and Tropical Diseases Hospital, University of Belgrade Teaching Hospital, Belgrade, Serbia. Mid dose (10-14 hours after dose) EFV plasma concentration was determined using a validated liquid chromatography/tandem mass spectrometry method. Genotyping for CYP2B6 516G>T (rs3745274), CYP2B6 c.485-18C>T (rs4803419), CAR c.540C>T (rs2307424), and CAR c.152-1089T>C (rs3003596) was conducted using allelic discrimination real-time polymerase chain reaction assay. One-way analysis of variance, Mann-Whitney test, Pearson or Spearman correlation, and multiple linear regression were used for data analysis.


RESULTS
Minor allele frequencies were similar to frequencies reported in other European populations. The overall mean (95% confidence interval) plasma EFV concentration was 2800 ng/mL (2460-3140). Significant differences between patients based on CYP2B6 516G>T (rs3745274) genotypes were observed: GG (n = 60), 2320 (range, 2160-2480) ng/mL; GT (n = 30), 3230 (range, 2790-3670) ng/mL; and TT (n = 2), 10,700 (range, 6170-15,300) ng/mL (P = 2.0 × 10). In multivariate linear regression analysis, CYP2B6 516G>T (rs3745274) [β = 1770 (1230 to 2310) ng/mL, P < 0.0001] and smoking status [β = -464 (-1250 to -43.3) ng/mL, P = 0.038] were independently associated with plasma EFV concentrations.


CONCLUSIONS
The effects of CYP2B6 516G>T (rs3745274) and smoking status on EFV plasma concentration in the Serbian population have been established for the first time.
*Department of Molecular and Clinical Pharmacology, University of Liverpool, United Kingdom; †Faculty of Pharmacy, Obafemi Awolowo University, Ile-Ife, Nigeria; ‡Infectious and Tropical Diseases Hospital, School of Medicine; and §Department of Pharmacology, Clinical Pharmacology and Toxicology, School of Medicine, University of Belgrade, Serbia.
Adeniyi
A
Olagunju
Marco
M
Siccardi
Alieu
A
Amara
Djordje
D
Jevtovic
Jovana
J
Kusic
Andrew
A
Owen
Gordana
G
Dragovic
D000328:Adult; D000480:Alkynes; D048588:Benzoxazines / Q000097:blood*; D015331:Cohort Studies; D003521:Cyclopropanes; D065702:Cytochrome P-450 CYP2B6 / Q000235:genetics*; D065695:Cytochrome P-450 CYP2B6 Inducers / Q000097:blood; D005260:Female; D015658:HIV Infections / Q000097:blood* / Q000453:epidemiology / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D055771:Serbia / Q000453:epidemiology; D012907:Smoking / Q000097:blood* / Q000453:epidemiology / Q000235:genetics*
D000480:Alkynes; D048588:Benzoxazines; D003521:Cyclopropanes; D065695:Cytochrome P-450 CYP2B6 Inducers; D065702:Cytochrome P-450 CYP2B6; C098320:efavirenz