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Title: Pharmacogenetic markers of CYP2B6 associated with efavirenz plasma concentrations in HIV-1 infected Thai adults
Authors: Chonlaphat Sukasem
Tim R. Cressey
Pattamawan Prapaithong
Yardpiroon Tawon
Ekawat Pasomsub
Chutatip Srichunrusami
Thawinee Jantararoungtong
Marc Lallement
Wasun Chantratita
Division of Pharmacogenomics and Personalized Medicine
Mahidol University
Chiang Mai University
Harvard School of Public Health
IRD Institut de Recherche pour le Developpement
Keywords: Medicine;Pharmacology, Toxicology and Pharmaceutics
Issue Date: 1-Dec-2012
Citation: British Journal of Clinical Pharmacology. Vol.74, No.6 (2012), 1005-1012
Abstract: Aims: To investigate the frequency of CYP2B6 polymorphisms and the influence of haplotype structure on plasma efavirenz concentrations in Thai adults with HIV-1 infection. Methods: Genotyping of nine single nucleotide polymorphisms (SNPs, c.64C > T, c.499C > G, c.516G > T, c.785A > G, c.1375A > G, c.1459C > T, g.3003T > C, g.18492C > T and g.21563C > T) of CYP2B6 were performed using real-time PCR-based allelic discrimination on blood samples from 52 HIV-infected adults who had received an efavirenz-based regimen. Plasma efavirenz concentrations were measured by high performance liquid chromatography. Results: The minor allele frequencies for c.64C > T, c.516G > T, c.785A > G, g.3003C > T, g.18492T > C and g.21563C > T were 0.087, 0.365, 0.413, 0.308 and 0.356, respectively. However, no variant alleles were identified for three SNPs (c.499 C > G, c.1375 A > G and c.1459 C > T). Efavirenz plasma concentrations were significantly associated with c.516G > T (P= 0.0095), c.785A > G (P= 0.0017), g.21563C > T (P= 0.0036) and g.18492C > T (P= 0.0011). The composite CYP2B6 of three SNPs (c.516G ≥ T, c.785A ≥ G and g.21563C ≥ T) genotypes were significantly associated with higher efavirenz concentrations. Conclusions: Our data indicate that the GAC-CYP2B6 haplotype is associated with higher plasma efavirenz concentrations in HIV-infected Thai adults. © 2012 The Authors. British Journal of Clinical Pharmacology © 2012 The British Pharmacological Society.
ISSN: 13652125
Appears in Collections:Scopus 2011-2015

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