Genetic Analysis of CYP2C9 with Reference to Drug Response in Epilepsy Patients of Pakistan.

IF 1.4 4区生物学 Q4 GENETICS & HEREDITY

Genetics research Pub Date : 2022-01-29 eCollection Date: 2022-01-01 DOI:10.1155/2022/1451007

Hafsa Maqbool, Tayyaba Saleem, Nadeem Sheikh, Aqsa Ashfaq

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引用次数: 2

Abstract

Epilepsy is a major global issue. Epilepsy patients are treated with AED (antiepileptic drugs). Interindividual variability in drug response has been documented in several studies. The resistance to drug response may be attributed to genetic polymorphism. The current study was undertaken to investigate the CYP2C9 gene polymorphism associated with antiepileptic drug (AED) resistance in the Pakistani population. The current study included 337 individuals including 100 control subjects, 110 drug-resistant subjects, and 127 drug responders. Genomic DNA was isolated from blood, and amplification of rs1799853 (430C > T) and rs1057910 was carried out by polymerase chain reaction. Genotypes of CYP2C9 SNPs were determined by Sanger's sequencing. Astounding results were observed in the current study that none of the well-known reported SNPs of CYP2C9 was found in our Pakistani cohorts. However, a novel missense variant (c.374G > A) was found only in drug-resistant patients of the current study. According to the in silico analysis performed by PolyPhen-2, it was observed that this nonsynonymous substitution is likely to be pathogenic. The results of our study demonstrated that rs1799853 and rs1057910 may be involved in drug resistance in the Pakistani population. However, some other variants on CYP2C9 may play a critical role in AED resistance that needs to be explored.

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巴基斯坦癫痫患者CYP2C9基因分析及药物反应参考

癫痫是一个重大的全球性问题。癫痫患者用抗癫痫药物治疗。药物反应的个体差异已在几项研究中得到证实。对药物反应的耐药可能与基因多态性有关。本研究旨在调查巴基斯坦人群中与抗癫痫药物(AED)耐药性相关的CYP2C9基因多态性。目前的研究包括337名个体，包括100名对照受试者，110名耐药受试者和127名药物应答者。从血中分离基因组DNA，采用聚合酶链反应扩增rs1799853 (430C > T)和rs1057910。采用Sanger测序法测定CYP2C9 snp的基因型。在当前的研究中观察到令人震惊的结果，在我们的巴基斯坦队列中没有发现已知的CYP2C9 snp。然而，仅在本研究的耐药患者中发现了一种新的错义变异(c.374G > a)。根据polyphen2进行的硅分析，观察到这种非同义替换可能是致病的。我们的研究结果表明rs1799853和rs1057910可能参与了巴基斯坦人群的耐药。然而，CYP2C9的其他一些变异可能在AED耐药中发挥关键作用，需要探索。

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来源期刊

Genetics research 生物-遗传学

自引率

6.70%

发文量

审稿时长

>12 weeks

期刊介绍： Genetics Research is a key forum for original research on all aspects of human and animal genetics, reporting key findings on genomes, genes, mutations and molecular interactions, extending out to developmental, evolutionary, and population genetics as well as ethical, legal and social aspects. Our aim is to lead to a better understanding of genetic processes in health and disease. The journal focuses on the use of new technologies, such as next generation sequencing together with bioinformatics analysis, to produce increasingly detailed views of how genes function in tissues and how these genes perform, individually or collectively, in normal development and disease aetiology. The journal publishes original work, review articles, short papers, computational studies, and novel methods and techniques in research covering humans and well-established genetic organisms. Key subject areas include medical genetics, genomics, human evolutionary and population genetics, bioinformatics, genetics of complex traits, molecular and developmental genetics, Evo-Devo, quantitative and statistical genetics, behavioural genetics and environmental genetics. The breadth and quality of research make the journal an invaluable resource for medical geneticists, molecular biologists, bioinformaticians and researchers involved in genetic basis of diseases, evolutionary and developmental studies.