Pharmacogene Variation in Thai Relapse Patients Treated with a Combination of Primaquine and Chloroquine.

Purpose: Pharmacogenes have an influence on biotransformation pathway and clinical outcome of primaquine and chloroquine which are often prescribed to treat 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 .

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 c.681G>A, the frequency of the A-allele that defines the non-functional haplotype was significantly higher compared to the G-allele (OR=5.14, =0.021). Patients heterozygous for c.421C>A had a higher odds ratio (OR=8.75, =0.071) and the frequency of the G-allele of .372G>A was higher compared to the A-allele (OR=3.75, =0.081). and 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 relapse. Further investigations are warranted to substantiate these findings.