MGB Block ARMS Real-Time PCR for Diagnosis of CYP2C19 Mutation in a Chinese Population

Author(s): Xi-Wen Jiang*, Yue Liu, Tao-Sheng Huang, Xiao-Ya Zhu

Journal Name: Current Bioinformatics

Volume 14 , Issue 5 , 2019

Become EABM
Become Reviewer

Graphical Abstract:


Background: CYP2C19 is an important genetic factor modulating clopidogrel dose requirement.

Objective: Therefore, a simple and economic genotyping method for predicting the clopidogrel dose of patients would be useful in clinical applications.

Methods: In this study, the MGB blocker ARMS real-time PCR contained two forward primers, two MGB blockers and a common reverse primer have been used for CYP2C19*2, *3 and *17 substitutions.

Results: Results showed that heterozygotes and homozygotes of CYP2C19*2, *3 and *17 could be distinguished by the MGB blocker ARMS real-time PCR successfully. In the Chinese population, patients with allele frequencies of CYP2C19*2, *3, and *17 are 18.43%, 3.03% and 0.76%, respectively.

Conclusion: This study indicates that the MGB blocker ARMS real-time PCR will be a simple, economical method for the rapid detection of SNPs in CYP2C19.

Keywords: MGB, blocker, ARMS, CYP2C19, genotyping, heterozygotes, homozygotes.

Uchiyama S. Clopidogrel resistance: identifying and overcoming a barrier to effective antiplatelet treatment. Cardiovasc Ther 2011; 29(6): e100-11.
Plosker GL, Lyseng-Williamson KA. Clopidogrel: a review of its use in the prevention of thrombosis. Drugs 2007; 67(4): 613-46.
Singh M, Thapa B, Arora R. Clopidogrel pharmacogenetics and its clinical implications. Am J Ther 2010; 17(3): e66-73.
Sofi F, Marcucci R, Gori AM, Giusti B, Abbate R, Gensini GF. Clopidogrel non-responsiveness and risk of cardiovascular morbidity. An updated meta-analysis. Thromb Haemost 2010; 103(4): 841-8.
Osnabrugge RL, Head SJ, Zijlstra F, et al. A systematic review and critical assessment of 11 discordant meta-analyses on reduced-function CYP2C19 genotype and risk of adverse clinical outcomes in clopidogrel users. Genet Med 2015; 17(1): 3-11.
Xie C, Ding X, Gao J, et al. The effects of CES1A2 A(-816)C and CYP2C19 loss-of-function polymorphisms on clopidogrel response variability among Chinese patients with coronary heart disease. Pharmacogenet Genomics 2014; 24(4): 204-10.
Langaee TY, Zhu HJ, Wang X, et al. The influence of the CYP2C19*10 allele on clopidogrel activation and CYP2C19*2 genotyping. Pharmacogenet Genomics 2014; 24(8): 381-6.
Owusu Obeng A, Egelund EF, Alsultan A, Peloquin CA, Johnson JA. CYP2C19 polymorphisms and therapeutic drug monitoring of voriconazole: are we ready for clinical implementation of pharmacogenomics? Pharmacotherapy 2014; 34(7): 703-18.
Harmsze A, van Werkum JW, Bouman HJ, et al. Besides CYP2C19*2, the variant allele CYP2C9*3 is associated with higher on-clopidogrel platelet reactivity in patients on dual antiplatelet therapy undergoing elective coronary stent implantation. Pharmacogenet Genomics 2010; 20(1): 18-25.
Harmsze AM, van Werkum JW, Ten Berg JM, et al. CYP2C19*2 and CYP2C9*3 alleles are associated with stent thrombosis: a case-control study. Eur Heart J 2010; 31(24): 3046-53.
Langaee TY, Zhu HJ, Wang X, et al. The influence of the CYP2C19*10 allele on clopidogrel activation and CYP2C19*2 genotyping. Pharmacogenet Genomics 2014; 24(8): 381-6.
Bennis Y, Bodeau S, Bouquié R, et al. High metabolic N-oxidation of voriconazole in a patient with refractory aspergillosis and CYP2C19*17/*17 genotype. Br J Clin Pharmacol 2015; 80(4): 782-4.
Abidi MZ, D’Souza A, Kuppalli K, Ledeboer N, Hari P. CYP2C19*17 genetic polymorphism-an uncommon cause of voriconazole treatment failure. Diagn Microbiol Infect Dis 2015; 83(1): 46-8.
Yasui-Furukori N, Takahata T, Nakagami T, et al. Different inhibitory effect of fluvoxamine on omeprazole metabolism between CYP2C19 genotypes. Br J Clin Pharmacol 2004; 57(4): 487-94.
Li M. Tetra-primer ARMS-PCR is an efficient SNP genotyping method: An example from SIRT2. Anal Methods 2014; 6(6): 1835-40.
Jafari M, Pirouzi A, Anoosheh S, Farnia P, Tajik N. Rapid and simultaneous detection of vitamin D receptor gene polymorphisms by a single ARMS-PCR assay. Mol Diagn Ther 2014; 18(1): 97-103.
Sediki FZ, Radoui A, Cabet F, Zemani-Fodil F, Saidi-Mehtar N, Boudjema A. Detection of CFTR mutations using PCR/ARMS in a sample of Algerian population. Ann Biol Clin 2014; 72(5): 549-54.
Guo SL, Chen XZ, Xiao YZ, et al. Use of the duplex TaqMan MGB probe for simultaneous detection of Perkinsus and Bonamia in marine shellfish. J Applied Oceanography 2014; 33(2): 284-9.
Tan HQ, Cai JS, Tan HF, et al. Establishment of quantitative real-time PCR targeting the MMS gene of Cronobacter spp. based on TaqMan-MGB probe. Zhongguo Shipin Weisheng Zazhi 2014.
Newton CR, Graham A, Heptinstall LE, et al. Analysis of any point mutation in DNA. The amplification refractory mutation system (ARMS). Nucleic Acids Res 1989; 17(7): 2503-16.

Rights & PermissionsPrintExport Cite as

Article Details

Year: 2019
Page: [391 - 399]
Pages: 9
DOI: 10.2174/1574893614666190109154252

Article Metrics

PDF: 28