Laboratory for Pharmacogenomics and Personalized Medicine, Department of Pathology, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand.
Br J Clin Pharmacol. 2012 Dec;74(6):1005-12. doi: 10.1111/j.1365-2125.2012.04288.x.
To investigate the frequency of CYP2B6 polymorphisms and the influence of haplotype structure on plasma efavirenz concentrations in Thai adults with HIV-1 infection.
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.
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.
Our data indicate that the GAC-CYP2B6 haplotype is associated with higher plasma efavirenz concentrations in HIV-infected Thai adults.
研究 CYP2B6 多态性的频率及其单倍型结构对泰国 HIV-1 感染成人患者体内依非韦伦血药浓度的影响。
采用实时 PCR 等位基因鉴别法对 52 例接受依非韦伦为基础方案治疗的 HIV 感染成人患者的血液样本进行 CYP2B6 9 个单核苷酸多态性（SNP，c.64C>T、c.499C>G、c.516G>T、c.785A>G、c.1375A>G、c.1459C>T、g.3003T>C、g.18492C>T 和 g.21563C>T）的基因分型。采用高效液相色谱法测定依非韦伦的血药浓度。
c.64C>T、c.516G>T、c.785A>G、g.3003C>T、g.18492T>C 和 g.21563C>T 的次要等位基因频率分别为 0.087、0.365、0.413、0.308 和 0.356。然而，三个 SNP（c.499C>G、c.1375A>G 和 c.1459C>T）未发现变异等位基因。依非韦伦血药浓度与 c.516G>T（P=0.0095）、c.785A>G（P=0.0017）、g.21563C>T（P=0.0036）和 g.18492C>T（P=0.0011）显著相关。三个 SNP（c.516G>T、c.785A>G 和 g.21563C>T）的复合 CYP2B6 基因型与较高的依非韦伦浓度显著相关。
我们的数据表明，GAC-CYP2B6 单倍型与泰国 HIV 感染成人患者体内较高的依非韦伦血药浓度有关。
