Division of Human Genetics, Faculty of Health Sciences, University of Cape Town Observatory, Cape Town, South Africa.
Front Genet. 2012 Nov 5;3:236. doi: 10.3389/fgene.2012.00236. eCollection 2012.
The ABCB1 gene encodes P-glycoprotein, an ATP-dependent drug efflux pump, which is responsible for drug transport across extra- and intra-cellular membranes. The variability in the expression of ABCB1 may contribute to variable plasma efavirenz concentration which results in variability in the levels of suppression of the human immunodeficiency syndrome virus (HIV). The aim of the study was to evaluate the role of polymorphisms in ABCB1 gene on plasma efavirenz levels and treatment response in the form of change in viral load and CD-4 cell count in HIV/AIDS patients receiving efavirenz-containing highly active antiretroviral treatment regimens. Two hundred and eighty-two HIV-infected patients were recruited from Themba Lethu Clinic in Johannesburg and plasma efavirenz drug concentration levels were measured using LC-MS/MS. SNaPshot was used to genotype five known ABCB1 single nucleotide polymorphisms (SNPs). Genotype-phenotype correlations were computed. The ABCB1 4036A/G and 4036G/G genotypes were significantly associated with low plasma efavirenz concentrations (P = 0.0236), while the ABCB1 1236C/T and 1236T/T genotypes were associated with high efavirenz concentrations (P = 0.0282). A haplotype ABCB1 T-G-T-A is reported that is associated with significantly increased plasma efavirenz levels. This is the first report on 61A>G, 2677G>T/A, and 4036A>G SNPs in the South African population. ABCB1 plays a role in determining the plasma concentrations of efavirenz and should be taken into account in future design of assays for genotype-based dosing of efavirenz-containing regimens.
ABCB1 基因编码 P-糖蛋白，一种 ATP 依赖性药物外排泵，负责将药物跨细胞内外膜转运。ABCB1 的表达变异性可能导致依非韦伦的血浆浓度变化，从而导致人类免疫缺陷病毒 (HIV) 的抑制水平变化。本研究旨在评估 ABCB1 基因多态性对接受依非韦伦为基础的高效抗逆转录病毒治疗方案的 HIV/AIDS 患者的血浆依非韦伦水平和治疗反应（以病毒载量和 CD4 细胞计数的变化形式）的作用。从约翰内斯堡 Themba Lethu 诊所招募了 282 名 HIV 感染患者，并使用 LC-MS/MS 测量血浆依非韦伦药物浓度水平。SNaPshot 用于检测五个已知的 ABCB1 单核苷酸多态性（SNP）的基因型。计算了基因型-表型相关性。ABCB1 4036A/G 和 4036G/G 基因型与低血浆依非韦伦浓度显著相关（P=0.0236），而 ABCB1 1236C/T 和 1236T/T 基因型与高依非韦伦浓度相关（P=0.0282）。报道了一种 ABCB1 T-G-T-A 单倍型，与血浆依非韦伦水平显著升高相关。这是南非人群中首次报道 61A>G、2677G>T/A 和 4036A>G SNP。ABCB1 在外排依非韦伦中起作用，在未来设计基于基因型的依非韦伦剂量测定的测定方法时应考虑到这一点。
