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. 2012 Dec;74(6):1005-12.
doi: 10.1111/j.1365-2125.2012.04288.x.

Pharmacogenetic markers of CYP2B6 associated with efavirenz plasma concentrations in HIV-1 infected Thai adults

Chonlaphat Sukasem  1 , Tim R Cressey, Pattamawan Prapaithong, Yardpiroon Tawon, Ekawat Pasomsub, Chutatip Srichunrusami, Thawinee Jantararoungtong, Marc Lallement, Wasun Chantratita
Affiliations

Pharmacogenetic markers of CYP2B6 associated with efavirenz plasma concentrations in HIV-1 infected Thai adults

Chonlaphat Sukasem et al. Br J Clin Pharmacol. 2012 Dec.

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.

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Figures

Figure 1
Figure 1
Impact of CYP2B6 polymorphisms; 516G>T (A), 785A>G (B), 18492T>C (C) and 21563C>T (1D) on efavirenz (EFV) plasma concentrations. Middle bar indicates the median and grey bar indicates the interquartile range. Mann–Whitney tests were used to compare efavirenz concentrations between two genotypes
Figure 2
Figure 2
Linkage disequilibrium of CYP2B6 for each polymorphism, data represents six SNPs in Haploview 4.2 software. Red quadrate without D' worth display mean D' = 1, LOD ≥2 while pale blue square mean D' = 1, LOD < 2; white quadrate, D' < 1 and LOD < 2; pale red square, D' < 1 and LOD ≥ 2
Figure 3
Figure 3
CYP2B6 GAC haplotype. Middle bar indicates the median and grey box indicates the interquartile range. Asterisks represent an individual subject
See this image and copyright information in PMC

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