Riaz Sana, Muhammad Din Sadia, Usman Tareen Muhammad, Tariq Fizza, Latif Yusra, Siddiqi Saima, Sultan Aneesa, Mansoor Atika
Institute of Biomedical and Genetic Engineering, 24 Mauve Area, G-9/1, Islamabad, Pakistan.
Department of Biochemistry, Faculty of Biological Sciences, Quaid-i-Azam University, Islamabad, Pakistan.
Iran J Pharm Res. 2019 Spring;18(2):1097-1102. doi: 10.22037/ijpr.2019.1100644.
CYP2C19 polymorphism is associated with pretreatment drug response prediction, metabolism, and disposition. Pakistan consists of a population comprising of various ethnic groups residing in different regions of the country each claiming diverse ethnic origins. The identification of CYP450 genotypic composition of these populations is therefore necessary to avoid adverse drug reactions in these individuals. The main objective of the study was to investigate the prevalence of CYP2C192 and CYP2C1917 alleles in these ethnic groups. The study was conducted on one thousand and twenty-eight (n = 1028) healthy volunteers from nine ethnic groups of Pakistan namely Brusho (n = 28), Hazara (n = 102), Kalash (n = 64), Pathan (n = 170), Punjabi (n = 218), Saraiki (n = 59), Brahui (n = 118), Parsi (n = 90), and Sindhi (n = 179). DNA was extracted from leukocytes and analyzed by allele specific amplification polymerase chain reaction (ASA-PCR). Multi allelic polymorphism of CYP2C19 led to four distinct phenotypes identified as extensive metabolizer (EM), poor metabolizer (PM), intermediate metabolizer (IM), and ultra-rapid metabolizer (UM). Over all, the percentage of predicted poor metabolizer allele was 29.0% compared to UM allele (23.70%). Among the studied groups, Saraiki and Brahui showed highest percentage of PM allele (40%, 36%) whereas Parsi and Hazara had highest percentage of UM allele (37% and 30% respectively). In conclusion, the high allele frequency of PM (CYP2C19*2 and *17) in Pakistani population led to the recommendation of a pre-treatment test to monitor drug response and dosage (personalized medicine) to avoid post-treatment adverse drug reactions.
细胞色素P450 2C19（CYP2C19）基因多态性与治疗前药物反应预测、代谢及处置相关。巴基斯坦人口由居住在该国不同地区的多个民族组成，每个民族都有不同的种族起源。因此，确定这些人群的细胞色素P450（CYP450）基因型组成对于避免这些个体出现药物不良反应很有必要。本研究的主要目的是调查这些民族中CYP2C192和CYP2C1917等位基因的流行情况。该研究对来自巴基斯坦9个民族的1028名健康志愿者进行，这些民族分别是布鲁肖族（n = 28）、哈扎拉族（n = 102）、卡拉什族（n = 64）、普什图族（n = 170）、旁遮普族（n = 218）、萨拉基族（n = 59）、俾路支族（n = 118）、帕西族（n = 90）和信德族（n = 179）。从白细胞中提取DNA，并通过等位基因特异性扩增聚合酶链反应（ASA-PCR）进行分析。CYP2C19的多等位基因多态性导致了四种不同的表型，分别被鉴定为快代谢型（EM）、慢代谢型（PM）、中间代谢型（IM）和超快代谢型（UM）。总体而言，预测的慢代谢型等位基因百分比为29.0%，而超快代谢型等位基因百分比为23.70%。在研究的群体中，萨拉基族和俾路支族的慢代谢型等位基因百分比最高（分别为40%和36%），而帕西族和哈扎拉族的超快代谢型等位基因百分比最高（分别为37%和30%）。总之，巴基斯坦人群中慢代谢型（CYP2C192和17）等位基因频率较高，因此建议进行治疗前检测以监测药物反应和剂量（个性化医疗），从而避免治疗后出现药物不良反应。
