Pearce Brendon, Abrahams-October Zainonesa, Xhakaza Lettilia, Jacobs Clifford, Benjeddou Mongi
Department of Biotechnology, University of the Western Cape, Cape Town, South Africa.
Department of Biotechnology, University of the Western Cape, Robert Sobukwe Road, Bellville 7535, Cape Town, South Africa.
Drug Metab Pers Ther. 2018 Jun 27;33(2):85-89. doi: 10.1515/dmpt-2017-0039.
Single nucleotide polymorphisms in promoter regions have been shown to alter the transcription of genes. Thus, SNPs in SLC22A2 can result in inter-individual variable response to medication.
The objective of the study was to investigate the effect of the African-specific promoter polymorphisms on the SLC22A2 gene expression levels in vitro. These included rs572296424 and rs150063153, which have been previously identified in the Xhosa population of South Africa. The promoter region (300 bp) for the two haplotypes was cloned into the pGLOW promoterless GFP reporter vector. The GFP expression levels of each haplotype was determined in the HEK293 cells using a GlowMax Multi-Detection E7031 luminometer in the form of light emission.
The relative promoter activity suggests that no significant variation exists between the expression levels of the WT and -95 haplotypes and the -95 and -156 haplotypes (p=0.498). However, the relative promoter activity of the WT haplotype in comparison to the -156 haplotype displayed a significant difference in expression level (p=0.016).
The data presented here show that the African-specific promoter polymorphisms can cause a decrease in the SLC22A2 gene expression levels in vitro, which in turn, may influence the pharmacokinetic profiles of cationic drugs.
启动子区域的单核苷酸多态性已被证明会改变基因的转录。因此，SLC22A2基因中的单核苷酸多态性可导致个体对药物的反应存在差异。
本研究的目的是在体外研究非洲特异性启动子多态性对SLC22A2基因表达水平的影响。这些多态性包括rs572296424和rs150063153，此前已在南非科萨族人群中被鉴定出来。将两种单倍型的启动子区域（300bp）克隆到无启动子的pGLOW绿色荧光蛋白报告载体中。使用GlowMax多检测E7031发光计以发光的形式在HEK293细胞中测定每种单倍型的绿色荧光蛋白表达水平。
相对启动子活性表明，野生型和-95单倍型以及-95和-156单倍型的表达水平之间不存在显著差异（p=0.498）。然而，与-156单倍型相比，野生型单倍型的相对启动子活性在表达水平上显示出显著差异（p=0.016）。
此处呈现的数据表明，非洲特异性启动子多态性可导致体外SLC22A2基因表达水平降低，进而可能影响阳离子药物的药代动力学特征。
