Wakil Salma M, Nguyen Cao, Muiya Nzioka P, Andres Editha, Lykowska-Tarnowska Agnieszka, Baz Batoul, Tahir Asma I, Meyer Brian F, Morahan Grant, Dzimiri Nduna
King Faisal Specialist Hospital and Research Centre, Riyadh 11211, Saudi Arabia.
The University of Western Australia, Perth, WA, Australia.
Dis Markers. 2015;2015:542543. doi: 10.1155/2015/542543. Epub 2015 Feb 22.
The Affymetrix Drug Metabolizing Enzymes and Transporters (DMET) Plus Premier Pack has been designed to genotype 1936 gene variants thought to be essential for screening patients in personalized drug therapy. These variants include the cytochrome P450s (CYP450s), the key metabolizing enzymes, many other enzymes involved in phase I and phase II pharmacokinetic reactions, and signaling mediators associated with variability in clinical response to numerous drugs not only among individuals, but also between ethnic populations.
We genotyped 600 Saudi individuals for 1936 variants on the DMET platform to evaluate their clinical potential in personalized medicine in ethnic Arabs.
Approximately 49% each of the 437 CYP450 variants, 56% of the 581 transporters, 56% of 419 transferases, 48% of the 104 dehydrogenases, and 58% of the remaining 390 variants were detected. Several variants, such as rs3740071, rs6193, rs258751, rs6199, rs11568421, and rs8187797, exhibited significantly either higher or lower minor allele frequencies (MAFs) than those in other ethnic groups.
The present study revealed some unique distribution trends for several variants in Arabs, which displayed partly inverse allelic prevalence compared to other ethnic populations. The results point therefore to the need to verify and ascertain the prevalence of a variant as a prerequisite for engaging it in clinical routine screening in personalized medicine in any given population.
Affymetrix药物代谢酶和转运体(DMET)Plus Premier芯片组旨在对1936个基因变异进行基因分型,这些变异被认为对个性化药物治疗中筛选患者至关重要。这些变异包括细胞色素P450(CYP450),即关键的代谢酶,许多参与I期和II期药代动力学反应的其他酶,以及不仅在个体之间,而且在不同种族人群之间与多种药物临床反应变异性相关的信号介质。
我们在DMET平台上对600名沙特人进行了1936个变异的基因分型,以评估它们在阿拉伯种族个性化医疗中的临床潜力。
检测到437个CYP450变异中的约49%、581个转运体中的56%、419个转移酶中的56%、104个脱氢酶中的48%以及其余390个变异中的58%。几个变异,如rs3740071、rs6193、rs258751、rs6199、rs11568421和rs8187797,其次要等位基因频率(MAF)显著高于或低于其他种族群体。
本研究揭示了阿拉伯人中几个变异的一些独特分布趋势,与其他种族人群相比,其等位基因流行率部分呈相反趋势。因此,结果表明有必要验证和确定变异的流行率,作为将其用于任何特定人群个性化医疗临床常规筛查的先决条件。