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

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.

p53/NF-kB Balance in SARS-CoV-2 Infection: From OMICs, Genomics and Pharmacogenomics Insights to Tailored Therapeutic Perspectives (COVIDomics)

“…These genes are highly polymorphic (e.g. CYP3A4/5 , CYP2B6 , CYP2C8 , CYP2C9 , CYP2C19 , CYP2D6 ) and are characterized by a wide geographic variability ( Zhou et al, 2017 ; Biswas et al, 2020 ; Sukprasong et al, 2021 ) interacting with large part of those drugs specifically used in COVID-19 ( Sukasem et al, 2013 ; Biswas et al, 2022 ). Interestingly, many clinical complications of COVID-19 belong to the same group of comorbidities responsible for the poor prognosis, and drugs acting as anti-inflammatory, antithrombotic (anti-coagulant and anti-aggregant), anti-hypertensive or with lipid-lowering action, have marked pharmacogenomics features resembling those belonging to the lipoproteins and homocysteine homeostasis genes ( Parmeggiani et al, 2008 ; Gemmati et al, 2009 ; Gemmati et al, 2016 ; Tisato et al, 2019 ; Cappadona et al, 2021 ; Tisato et al, 2021 ; Biswas et al, 2022 ).…”

Pharmacogenetics and Precision Medicine Approaches for the Improvement of COVID-19 Therapies

“…It has been previously reported that ~25% of the Thai population carried HLA-DQA1/ HLA-DQB1 genetic polymorphisms (Puangpetch et al, 2014; .5, and 1.8%, respectively. Approximately 30% of the CYP3A4 variant allele was identified in the Thai population as reported elsewhere (Sukprasong et al, 2021). Over 30% Thai population carried C3435T ABCB1 genetic polymorphisms as revealed in a previous study conducted in Thailand (Sensorn et al, 2013).…”

“…The most prevalent and studied genetic variants of the CYP3A4/5, CYP2B6, CYP2C8, CYP2C9, CYP2C19, and CYP2D6 pharmacogenes have wide inter-ethnic variability. For example, CYP2D6*4 is highly prevalent in American population, whereas CYP2C19*2, *3 is highly prevalent in South Asians (Sukasem et al, 2013;Medhasi et al, 2016;Zhou et al, 2017;Biswas, 2021a;Sukprasong et al, 2021).…”

Introduction of new alternative pipeline using multiplexed fast COLD‑PCR together with sequencing approach highlighting pharmacoeconomics by detection of CYP variants

“…The performance evaluation showed notable results in this single system. The following estimated frequencies were obtained in our Thai-population-focused study: 3.7% in CYP2C9*2 and CYP2C19*3, 55.5% in CYP2C19*2, 77.7% in CYP2D6*10, and 14.8% in CYP2D6* 41. In previous studies, frequencies of only 0.08% for CYP2C9*2, 25.6% for CYP2C19*2 and 2.5% for CYP2C19*3 alleles were found in a Thai population (26,41). For CYP2D6 in Thai population, the decreased-function allele CYP2D6*10 is the most common allele found in patients treated with risperidone, at 51.8%, followed by CYP2D6*41 at 6.8% (42).…”