Validation of a multi-gene qPCR-based pharmacogenomics panel across major ethnic groups in Singapore and Indonesia

Abstract

AbstractBackgroundWith up to 70% of adverse drug reactions (ADRs) having high genetic associations, the clinical utility of pharmacogenomics (PGx) has been gaining traction. Nala PGx Core™ is a multi-gene qPCR-based panel that comprises 18 variants and 2 CYP2D6 Copy Number markers across 4 pharmacogenes – CYP2C9, CYP2C19, CYP2D6 and SLCO1B1.ObjectivesIn this study, we validated the performance of Nala PGx Core™ against benchmark methods, on the Singaporean and Indonesian populations. Additionally, we examined the allele and diplotype frequencies across 5 major ethnic groups present in these populations namely, Indonesians, Chinese, Malays, Indians and Caucasians.MethodsHuman gDNA samples, extracted from the buccal swabs of 246 participants, were tested on Nala PGx Core™ and two chosen benchmarks, Agena VeriDose® Core and CYP2D6 Copy Number Variation (CNV) Panel, and TaqMan® DME Genotyping Assays. Performance was evaluated based on assay robustness, precision and accuracy at the genotype- and diplotype-level.ResultsNala PGx Core™ demonstrated high genotype- and diplotype-level call rates of >97% and >95% respectively in CYP2D6, and 100% for CYP2C9, CYP2C19 and SLCO1B1. A precision rate of 100% was observed on both intra- and inter-precision studies. Variant-level concordance to the benchmark methods was ≥96.9% across all assays, which consequently resulted in a diplotype-level concordance of ≥94.7% across CYP2C9, CYP2C19 and CYP2D6. Overall, the allele frequencies of CYP2D6*10 and CYP2D6*36 were higher in our cohort as compared to previous records. Notably, CYP2D6 copy number variation (CNV) analysis demonstrated a CYP2D6 *10/*36 frequency of 26.5% amongst the Indonesian cohort.ConclusionNala PGx Core™ produced robust and accurate genotyping when compared to other established benchmarks. Furthermore, the panel successfully characterized alleles of clinical relevance in the Singaporean and Indonesian populations such as CYP2D6*10 and CYP2D6*36, suggesting its potential for adoption in clinical workflows regionally.