Pharmacogene variation in Thai Plasmodium vivax relapse patients treated with a combination of primaquine and chloroquine
Journal Title
Pharmacogenomics and Personalized Medicine
Publication Type
Journal Article
Abstract
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((R)) and Taqman((R)) 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.
Publisher
Dove Press
WEHI Research Division(s)
Population Health And Immunity
PubMed ID
32021383
Open Access at Publisher's Site
https://doi.org/10.2147/PGPM.S201007
Rights Notice
Refer to copyright notice on published article.


Creation Date: 2020-05-04 11:46:49
Last Modified: 2020-05-04 01:49:58
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