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Title: Pharmacogene variation in Thai Plasmodium vivax relapse patients treated with a combination of primaquine and chloroquine
Authors: Monpat Chamnanphon
Andrea Gaedigk
Apichaya Puangpetch
Ekawat Pasomsub
Wasun Chantratita
Rhea J. Longley
Jetsumon Sattabongkot
Pajaree Chariyavilaskul
Chonlaphat Sukasem
Chulalongkorn University
Walter and Eliza Hall Institute of Medical Research
University of Melbourne
Faculty of Medicine, Ramathibodi Hospital, Mahidol University
Mahidol University
University of Missouri-Kansas City
Keywords: Biochemistry, Genetics and Molecular Biology;Pharmacology, Toxicology and Pharmaceutics
Issue Date: 1-Jan-2020
Citation: Pharmacogenomics and Personalized Medicine. Vol.13, (2020), 1-12
Abstract: © 2020 Chamnanphon et al. Purpose: Pharmacogenes have an influence on biotransformation pathway and clinical outcome of primaquine and chloroquine which are often prescribed to treat Plasmodium vivax infection. Genetic variation may impact enzyme activity and/or transporter function and thereby contribute to relapse. The aim of the study was to assess allele, genotype frequencies and the association between pharmacogenes variation and primaquine response in Thai patients infected with Plasmodium vivax. Patients and Methods: Fifty-one patients were genotyped for 74 variants in 18 genes by Sequenom MassARRAY® and Taqman® SNP Real-Time PCR. Results: SNP frequencies were not significantly different between relapse (n=4) and non-relapse (n=47) patients. However, the CYP2C19 c.681G>A, the frequency of the A-allele that defines the non-functional CYP2C19*2 haplotype was significantly higher compared to the G-allele (OR=5.14, p=0.021). Patients heterozygous for ABCG2 c.421C>A had a higher odds ratio (OR=8.75, p=0.071) and the frequency of the G-allele of UGT2B7 c.372G>A was higher compared to the A-allele (OR=3.75, p=0.081). CYP2C19, ABCG2 and UGT2B7 emerged as potential high priority genes. Conclusion: Decreased activity of CYP2C19, ABCG2 and UGT2B7 in combination with CYP2D6 intermediate or poor metabolizer status may expose patients to a higher risk of Plasmodium vivax relapse. Further investigations are warranted to substantiate these findings.
ISSN: 11787066
Appears in Collections:Scopus 2020

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