Afilal Driss, Basselam Mohamed Amine, Brakez Zahra, Chouham Said, Brehm António, Izaabel El Hassan
1 Cellular Biology and Molecular Genetics Laboratory, Faculty of Sciences, University Ibn-Zohr , Agadir, Morocco .
2 Human Genetics Laboratory, Life Sciences Faculty, University of Madeira , Funchal, Portugal .
Genet Test Mol Biomarkers. 2017 May;21(5):298-304. doi: 10.1089/gtmb.2016.0304. Epub 2017 Mar 10.
The polymorphic cytochrome P450 isoenzymes CYP2C9 and CYP2C19 are involved in the biotransformation of a wide variety of clinical drugs. Their major alleles occur with varying frequencies among different populations worldwide and have been associated with a varied capacity to degrade important therapeutic agents. This gives rise to important individual and interethnic variability in drug metabolism and may be the cause for different clinical responses regarding drug administration. In this study we aimed to analyze the distribution of the CYP2C9 and CYP2C19 major alleles associated with the impaired metabolism, and that account for the "poor metabolizer" phenotype in our study population.
A sample of 290 healthy subjects living in South Morocco was genotyped using a restriction fragment length polymorphism-polymerase chain reaction genotyping method.
The CYP2C93 and CYP2C193 mutations were not found in our population. The CYP2C92 and CYP2C192 were the most common alleles, respectively with frequencies of 8% and 11.4%. Regarding CYP2C92 and CYP2C192, approximately 16% and 22% of Moroccans are respectively deficient metabolizers, and thus largely lack this enzymatic activity. Our results suggest that only CYP2C92 and CYP2C192 are likely to substantially contribute to individual and interethnic variability of CY2C9-19 activity in our population.
The distribution of clinically relevant alleles of the CYP2C19 and CYP2C9 genes among our population follows the patterns commonly found in other Mediterranean populations, and suggests a certain degree of African influence. This population study provides relevant information on polymorphisms within the CYP2C19 and CYP2C9 genes. In the future, these results could be used in prognosis and for predicting response to drug treatments as well as to help develop personalized medicine studies in the Moroccan population.
多态性细胞色素P450同工酶CYP2C9和CYP2C19参与多种临床药物的生物转化。它们的主要等位基因在全球不同人群中的出现频率各异，并与降解重要治疗药物的能力差异有关。这导致了药物代谢中重要的个体和种族间差异，可能是药物给药后出现不同临床反应的原因。在本研究中，我们旨在分析与代谢受损相关的CYP2C9和CYP2C19主要等位基因的分布情况，这些等位基因构成了我们研究人群中的“代谢不良者”表型。
使用限制性片段长度多态性-聚合酶链反应基因分型方法对290名生活在摩洛哥南部的健康受试者样本进行基因分型。
我们的人群中未发现CYP2C93和CYP2C193突变。CYP2C92和CYP2C192是最常见的等位基因，频率分别为8%和11.4%。关于CYP2C92和CYP2C192，约16%和22%的摩洛哥人分别为代谢缺陷者，因此很大程度上缺乏这种酶活性。我们的结果表明，只有CYP2C92和CYP2C192可能在很大程度上导致我们人群中CY2C9 - 19活性的个体和种族间差异。
CYP2C19和CYP2C9基因的临床相关等位基因在我们人群中的分布遵循其他地中海人群中常见的模式，并显示出一定程度的非洲影响。这项人群研究提供了关于CYP2C19和CYP2C9基因多态性的相关信息。未来，这些结果可用于预后评估、预测药物治疗反应，以及帮助开展摩洛哥人群的个性化医学研究。
