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Prevalence of CYP2C19, CYP3A4 and FMO3 genetic polymorphisms in healthy northeastern Thai volunteers

Thikhumporn Areesinpitak, Sirimas Kanjanawart, Nontaya Nakkam, Wichittra Tassaneeyakul, Suda Vannaphasaht^*

 
ABSTRACT:     Voriconazole is the first-line drug for invasive aspergillosis infection treatment. It is metabolized via cytochrome P450 2C19 (CYP2C19), cytochrome P450 3A4 (CYP3A4) and flavin-containing monooxygenase 3 (FMO3). Many studies revealed the correlation between genetic polymorphisms of these SNPs and voriconazole metabolism. Several mutations, however, have not been reported in Thai population. Therefore, this study investigated the prevalence of CYP2C19, CYP3A4 and FMO3 polymorphisms. Two hundred and forty-nine healthy northeastern Thai volunteers who were blood donors at Srinagarind Hospital blood bank were enrolled. CYP2C19 (*2, *3, *17), CYP3A4 (*22, rs4646437G>A) and FMO3 (rs2266782G>A, rs2266780A>G) mutations were investigated. The allele frequencies were CYP2C19*1 (0.72), *2 (0.24), *3 (0.03) and *17 (0.02) in this study. They were significantly different from Caucasian and Japanese populations. Moreover, CYP3A4 rs4646437 allele frequencies were 0.76 for “G” and 0.24 for “A” alleles. The mutation of CYP3A4*22 was not found in this study. Wild type (G) and mutation (A) allele frequencies of FMO3 rs2266782 were 0.86 and 0.14, respectively. Similarly, the allele frequencies of FMO3 rs2266780 for “A” (wild type) and “G” (mutant) were 0.89 and 0.11, respectively. Furthermore, a strong linkage disequilibrium was found between FMO3 rs2266782 and rs2266780 genes (D^' = 0.955, r² = 0.7021). The information on the SNP frequencies of CYP2C19, CYP3A4 and FMO3 in Thais was found to be significantly different from other populations. The genotype prevalence may be the preliminary information for a further clinical study to investigate the association between these genotypes and voriconazole treatment outcomes.

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* Corresponding author, E-mail: sudvan@kku.ac.th

Received 13 Aug 2019, Accepted 23 May 2020