Allele frequencies of single nucleotide polymorphisms of clinically important drug-metabolizing enzymes CYP2C9, CYP2C19, and CYP3A4 in a Thai population

Rattanaporn Sukprasong,Nutthan Nuntharadthanaphong,Napatrupron Koomdee,Santirhat Prommas,Chonlaphat Sukasem,Apichaya Puangpetch,Nutcha Jongjitsook,Sumonrat Chuwongwattana,Pimonpan Jinda,Jiratha Rachanakul,Thawinee Jantararoungtong

doi:10.1038/s41598-021-90969-y

Allele frequencies of single nucleotide polymorphisms of clinically important drug-metabolizing enzymes CYP2C9, CYP2C19, and CYP3A4 in a Thai population

Rattanaporn Sukprasong, Nutthan Nuntharadthanaphong + Show 9 more

Open Access

https://doi.org/10.1038/s41598-021-90969-y

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Abstract

Prior knowledge of allele frequencies of cytochrome P450 polymorphisms in a population is crucial for the revision and optimization of existing medication choices and doses. In the current study, the frequency of the CYP2C9*2, CYP2C9*3, CYP2C19*2, CYP2C19*3, CYP2C19*6, CYP2C19*17, and CYP3A4 (rs4646437) alleles in a Thai population across different regions of Thailand was examined. Tests for polymorphisms of CYP2C9 and CYP3A4 were performed using TaqMan SNP genotyping assay and CYP2C19 was performed using two different methods; TaqMan SNP genotyping assay and Luminex x Tag V3. The blood samples were collected from 1205 unrelated healthy individuals across different regions within Thailand. Polymorphisms of CYP2C9 and CYP2C19 were transformed into phenotypes, which included normal metabolizer (NM), intermediate metabolizer (IM), poor metabolizer (PM), and rapid metabolizers (RM). The CYP2C9 allele frequencies among the Thai population were 0.08% and 5.27% for the CYP2C9*2 and CYP2C9*3 alleles, respectively. The CYP2C19 allele frequencies among the Thai population were 25.60%, 2.50%, 0.10%, and 1.80% for the CYP2C19*2, CYP2C19*3, CYP2C19*6, and CYP2C19*17 alleles, respectively. The allele frequency of the CYP3A4 (rs4646437) variant allele was 28.50% in the Thai population. The frequency of the CYP2C9*3 allele was significantly lower among the Northern Thai population (P < 0.001). The frequency of the CYP2C19*17 allele was significantly higher in the Southern Thai population (P < 0.001). Our results may provide an understanding of the ethnic differences in drug responses and support for the utilization of pharmacogenomics testing in clinical practice.

Highlights

Genetic variations exist across different human populations and are often associated with the variation of drug response between p opulations[1]
For the allele frequency of CYP2C9, CYP2C19, and CYP3A4 polymorphisms, a total of 1,205 blood specimens of unrelated healthy donors were obtained from the Thai National Health Examination Survey
Numerous studies have analyzed the frequencies of the polymorphisms in CYP2C9, CYP2C19, and CYP3A4 in the Thai population; yet the available frequency data have been derived from a small sample of the Thai population

Summary

Introduction

Genetic variations exist across different human populations and are often associated with the variation of drug response between p opulations[1]. Genetic polymorphisms in phase-1 drug-metabolizing enzymes, such as cytochrome P450 oxidases (CYPs), can alter the pharmacokinetic properties of the administered drugs, their metabolites, or both at the target site, resulting in variability in drug responses[3]. The CYP2C9*2 (R144C) and CYP2C9*3 (I359L) alleles are the clinically relevant defective variants associated with decreased enzyme activity and impaired drug metabolism phenotypes. The frequency of CYP2C9*2 is 12.68% in European, 4.60% in South Asian, 2.35% in African, and < 1% in East Asian ancestry. The frequency of CYP2C9*3 is 11.31% in South Asian, 6.88% in European, 3.38% in East Asian, and 1.26% in African a ncestry[6]. The allelic frequencies of CYP2C19*2 and CYP2C19*3 responsible for the majority of PM phenotypes in the metabolism of CYP2C19 substrate drugs are higher in Asian p opulations[9]

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Discussion

Conclusion