Comprehensive analysis of important pharmacogenes in Koreans using the DMET™ platform

Abstract

Genetic polymorphisms of enzymes and transporters associated with the absorption, distribution, metabolism, and elimination (ADME) of drugs are one of the major factors that contribute to interindividual variations in drug response. In the present study, we aimed to elucidate the pharmacogenetic profiles of the Korean population using the Affymetrix Drug Metabolizing Enzyme and Transporters (DMET™) platform. A total of 1,012 whole blood samples collected from Korean subjects were genotyped using the DMET™ plus microarray. In total, 1,785 single nucleotide polymorphism (SNP) markers for 231 ADME genes were identified. The genotype and phenotype of 13 clinically important ADME genes implemented in the Clinical Pharmacogenetics Implementation Consortium guidelines were compared among different ethnic groups. Overall, the genotype frequencies of the Korean population were similar to those of the East Asian population. Several genes, notably CYP2C19 and VKORC1 , showed marked differences in Koreans compared to Europeans (EURs) or Africans (AFRs). The percentage of CYP2C19 poor metabolizers was 15% in Koreans and less than 3% in EURs or AFRs. The frequencies of causative SNPs of the VKORC1 gene for the low warfarin dose phenotype were 90%, 60%, and 10% in Koreans, EURs and AFRs, respectively. Our findings can be utilized for optimal pharmacotherapy in Korean patients.

Frequency of the CYP2C19*10 Allele in the Korean Population

“…In the present study, we observed to following allele frequencies: 63.0% for CYP2C19*1, 26.4% for CYP2C19*2, 9.4% for CYP2C19*3, and 1.3% for CYP2C19*17. The frequency of the CYP2C19*17 allele was similar to that reported by other Korean (0.3%-1.5%) or Asian (0.5%-3%) studies, and was lower than that reported for Caucasians (15.4%-33.8%) or Africans (10%-18%) (Sim et al 2006;Kim et al 2010;Li-Wan-Po et al 2010;Ramsjö et al 2010;Scott et al 2011;Kim et al 2021). Based on the ability to metabolize CYP2C19 substrates, individuals are categorized into the five phenotype categories recommended by the Clinical Pharmacogenetics Implementation Consortium (CPIC), as follows: PMs, IMs, NMs; formerly known as extensive metabolizers (EM), RMs, and ultrarapid metabolizers (Caudle et al 2017;Lee et al 2022).…”

“…Although reports of the frequency of the CYP2C19*10 allele are scarce, it exhibited a low frequency of less than 1% (Table 3) (Nakamoto et al 2007;Rasmussen and Werge 2008;Langaee et al 2014;Khalil et al 2016;Kim et al 2021;Goljan et al 2022).…”

Estimation of the benefit from pre‐emptive genotyping based on the nationwide cohort data in South Korea

“…For example, the indirect cost of acute myocardial infarction in Korea accounted for 42.3% of the total costs in 2012 31 . Therefore, the calculated benefit in our study would be the minimal estimate but could suggest implementing cost‐effective genotype panels 32 …”

“…31 Therefore, the calculated benefit in our study would be the minimal estimate but could suggest implementing cost-effective genotype panels. 32 The cost-effectiveness of pre-emptive genotyping compared to reactive genotyping is still on debate. Reactive genotyping is easier to perform and has already shown cost-effectiveness.…”

“… 31 Therefore, the calculated benefit in our study would be the minimal estimate but could suggest implementing cost‐effective genotype panels. 32 …”