Detection Of Cyp2c9 And Cyp2c19 Single Nucleotide Polymorphisms (Snps) Among Aboriginal Jahai And Malay Populations In Malaysia
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Date
2016-03
Authors
Rosdi, Rasmaizatul Akma
Journal Title
Journal ISSN
Volume Title
Publisher
Universiti Sains Malaysia
Abstract
CYP2C9 and CYP2C19 are highly polymorphic genes in cytochrome P450 (CYP). They encode enzymes that catalyze the biotransformation of many drugs such as S-warfarin, nonsteroidal anti-inflammatory drugs (NSAIDS), antitumor and antimalarial. However, polymorphisms in the genes affect the efficacy and toxicity of the drugs inter-individually or inter-ethnically. Hence, the objective of the study is to investigate the single nucleotide polymorphisms (SNPs) of CYP2C9 and CYP2C19 genes using nested allele-specific multiplex polymerase chain reaction (PCR) and high resolution melting (HRM) methods among aboriginal people of Jahai and Malays in Malaysia respectively. Moreover, it is also to develop an HRM genotyping method for CYP2C19 SNPs detection. This study was approved by the Research and Ethics Committee of USM. Genomic DNAs were extracted from whole blood of 155 Jahais and 183 Malays using the commercialized extraction kit. The DNA was subjected to PCR method for four CYP2C9 SNPs. While the HRM technique was used to genotype another four of CYP2C19 SNPs. Direct DNA sequencing analysis was performed to validate the genotyping results. Four SNPs were found in Jahai; CYP2C9*3, CYP2C19*2, CYP2C19*3 and CYP2C19*17 and appeared to be significantly differences with Malays. CYP2C9*2 allele frequency was only found in Malay, however, was not different significantly with Jahai. The allelic frequency of CYP2C9*3 in Jahai was 36.2% making them the highest allele carriers thus far in Southeast Asia. The developed HRM method had showed 100% robust, sensitive and specific as CYP2C19 SNPs genotyping method.
Besides, it also demonstrated to be more rapid, time saving and less laborious than PCR method. According to the genotyping results obtained, Jahai may need the drug dosage adjustment of the particular drugs. Meanwhile, HRM is more suitable to be used in daily clinical setting to detect the gene polymorphisms. By investigating the polymorphisms in the gene, it will help to determine more appropriate drug dosage and reduce adverse drug reactions in individual or ethnic.
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Keywords
Single nucleotide polymorphisms , among aboriginal people of Jahai.