Du Plessis Morne, Pearce Brendon, Jacobs Clifford, Hoosain Nisreen, Benjeddou Mongi
Department of Biotechnology, University of the Western Cape, Robert Sobukwe Road, Bellville, Cape Town, 7535, South Africa.
Mol Biol Rep. 2015 Mar;42(3):665-72. doi: 10.1007/s11033-014-3813-2. Epub 2014 Nov 15.
Human organic cation transporter 1 (hOCT1) is expressed primarily in hepatocytes and mediate the electrogenic transport of various endogenous and exogenous compounds, including clinically important drugs. Genetic polymorphisms in the gene coding for hOCT1, SLC22A1, are increasingly being recognized as a possible mechanism explaining the variable response of individual patients to clinical drugs which are substrates for this transporter. The aim of this study was to investigate the allele and genotype frequencies of single-nucleotide polymorphisms (SNPs) of SLC22A1 in the Cape Admixed population of South Africa. The genotypic and allelic distributions of nineteen nonsynonomous and one intronic SLC22A1 SNPs were determined in 100 healthy Cape Admixed participants, using a SNaPshot(®) multiplex assay. In addition, haplotype structure for SLC22A1 was inferred from the genotypic data. The minor allele frequencies for S14F, P341L, S189L, G220V, V519F, M440I, G465R and the rs622342 intronic variant were 1.0, 0.5, 1.0, 1.0, 1.5, 0.5, 0.5 and 18.0%, respectively. None of the participants carried the variant allele for R61C, C88R, P283L, R287G and G401S. In addition, no variant alleles were observed for A306T, A413V, M420V, I421F, C436F, V501E, and I542V in the population. Twelve haplotypes were inferred from the genotypic data. The frequencies for most common haplotypes CCTCGGCGCGCTAGAGCTGA, CCTCGGCGCGCTAGCGCTGA and CCTCGGCGCGCGAGCGCTGA were 80, 9.9, and 3.5%, respectively.
人类有机阳离子转运体1(hOCT1)主要在肝细胞中表达,并介导各种内源性和外源性化合物的电转运,包括临床上重要的药物。编码hOCT1的基因SLC22A1中的遗传多态性越来越被认为是解释个体患者对作为该转运体底物的临床药物反应差异的一种可能机制。本研究的目的是调查南非开普混血人群中SLC22A1单核苷酸多态性(SNP)的等位基因和基因型频率。使用SNaPshot®多重分析法在100名健康的开普混血参与者中确定了19个非同义SLC22A1 SNP和1个内含子SNP的基因型和等位基因分布。此外,从基因型数据推断出SLC22A1的单倍型结构。S14F、P341L、S189L、G220V、V519F、M440I、G465R和rs622342内含子变体的次要等位基因频率分别为1.0%、0.5%、1.0%、1.0%、1.5%、0.5%、0.5%和18.0%。没有参与者携带R61C、C88R、P283L、R287G和G401S的变异等位基因。此外,在该人群中未观察到A306T、A413V、M420V、I421F、C436F、V501E和I542V的变异等位基因。从基因型数据推断出12种单倍型。最常见的单倍型CCTCGGCGCGCTAGAGCTGA、CCTCGGCGCGCTAGCGCTGA和CCTCGGCGCGCGAGCGCTGA的频率分别为80%、9.9%和3.5%。