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Please use this identifier to cite or link to this item: http://repository.li.mahidol.ac.th/dspace/handle/123456789/45944
Title: Real time PCR detection of common CYP2D6 genetic variants and its application in a Karen population study 06 Biological Sciences 0604 Genetics
Authors: Kanokpich Puaprasert
Cindy Chu
Naowarat Saralamba
Nicholas P.J. Day
Francois Nosten
Nicholas J. White
Arjen M. Dondorp
Mallika Imwong
Mahidol University
Nuffield Department of Clinical Medicine
Keywords: Immunology and Microbiology;Medicine
Issue Date: 15-Nov-2018
Citation: Malaria Journal. Vol.17, No.1 (2018)
Abstract: © 2018 The Author(s). Background: Plasmodium vivax malaria is characterized by relapses arising from the hypnozoite stages in the liver. The only currently registered drug for radical treatment to prevent relapse is primaquine. Primaquine, a prodrug, requires metabolism through the liver cytochrome CYP2D6 isoenzyme to its active metabolite. Mutations in the CYP2D6 gene may thus affect primaquine efficacy. A SNPs genotyping technique was developed to characterize the CYP2D6 genetic variants and tested this in the patients with Plasmodium vivax infection collected in a Karen population on the Thailand-Myanmar border, where P. vivax malaria is endemic. Methods: Direct sequencing of PCR-reamplified products (DSP) was used to uncover exonic CYP2D6 sequence variations. Subsequently, an allele-specific oligonucleotide probe real-time SNPs genotyping (ASO) assay was developed for rapid detection of the four clinically relevant CYP2D6 variants occurring in this population. These two in-house developed assays were used to genotype CYP2D6 mutations in blood samples obtained from 70 Karen adults. Results: Results showed a high degree of concordance between the DSP and ASO methods. Six CYP2D6 point mutations were identified within the Karen population: C100T, C1039T, G1661C, G1846A, C2850T and G4180C, at frequencies of 0.43, 0.43, 0.76, 0.02, 0.32 and 0.76, respectively. The CYP2D6∗2,∗4,∗5,∗10 and∗36 allelic frequencies were 0.33, 0.02, 0.03, 0.40 and 0.01, respectively. Alleles conferring an intermediate CYP2D6 metabolizer phenotype comprised 46% of the total number of alleles. Conclusion: The newly developed ASO assay is a reliable and rapid tool for large-scale CYP2D6 genotyping. The high frequency of the CYP2D6∗10 allele in the Karen population warrants further assessment of its association with the radical curative efficacy of primaquine.
URI: https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85056624122&origin=inward
http://repository.li.mahidol.ac.th/dspace/handle/123456789/45944
ISSN: 14752875
Appears in Collections:Scopus 2018

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