Actionable pharmacogenetic variants in Hong Kong Chinese exome sequencing data and projected prescription impact in the Hong Kong population

Abstract

Preemptive pharmacogenetic testing has the potential to improve drug dosing by providing point-of-care patient genotype information. Nonetheless, its implementation in the Chinese population is limited by the lack of population-wide data. In this study, secondary analysis of exome sequencing data was conducted to study pharmacogenomics in 1116 Hong Kong Chinese. We aimed to identify the spectrum of actionable pharmacogenetic variants and rare, predicted deleterious variants that are potentially actionable in Hong Kong Chinese, and to estimate the proportion of dispensed drugs that may potentially benefit from genotype-guided prescription. The projected preemptive pharmacogenetic testing prescription impact was evaluated based on the patient prescription data of the public healthcare system in 2019, serving 7.5 million people. Twenty-nine actionable pharmacogenetic variants/ alleles were identified in our cohort. Nearly all (99.6%) subjects carried at least one actionable pharmacogenetic variant, whereas 93.5% of subjects harbored at least one rare deleterious pharmacogenetic variant. Based on the prescription data in 2019, 13.4% of the Hong Kong population was prescribed with drugs with pharmacogenetic clinical practice guideline recommendations. The total expenditure on actionable drugs was 33,520,000 USD, and it was estimated that 8,219,000 USD (24.5%) worth of drugs were prescribed to patients with an implicated actionable phenotype. Secondary use of exome sequencing data for pharmacogenetic analysis is feasible, and preemptive pharmacogenetic testing has the potential to support prescription decisions in the Hong Kong Chinese population.

HKG: an open genetic variant database of 205 Hong Kong cantonese exomes

“…Owing to the increasing need to gather genetic data for population-wide studies, Yu et al. recently analyzed the WES data of 1,116 Hong Kong samples and identified a set of variants for potential pharmacogenetic use in Hong Kong ( 15 ). Most of their variant data, however, are not publicly available.…”

Systematic Review of Pharmacogenetic Factors That Influence High-Dose Methotrexate Pharmacokinetics in Pediatric Malignancies

“…PK findings from clinical studies can lead to improvements in therapeutic outcomes through amendments to clinical protocols [ 5 , 15 ] or the development of clinical decision support tools [ 16 ]. It was recently shown that >90% of persons have an actionable drug-gene polymorphism [ 17 , 18 ]. A plethora of clinical studies have been including pharmacogenetics in an effort to describe more of the variability in MTX PK and improve therapeutic outcomes.…”

Cancer Pharmacogenetics: perspective on newly discovered and implemented predictive biomarkers

“…Integrating rare genetic variants into pre-emptive pharmacogenetic tests will allow genotyping to be highly effective for a true individualization of patients' drug treatment regimens (33). Besides understanding which drug would fully benefi t from a pharmacogene characterization at the sequencing level, population-specifi c patterns of rare variants should be known (34,35) and taken into consideration for developing population-adjusted genetic profi ling strategies (2,36,37). For instance, CPIC guidelines recommended TPMT and NUDT15 genotyping of common variants for thiopurine dosing.…”

“…In other populations, such as in the Europeans, the characterization of variants in TPMT should be a priority (39). Cost-effectiveness of the analysis of rare variants in pharmacogenes has still to be clearly estimated, however NGS costs have been consistently reducing in recent years and this approach is promising for the future pharmacogenomic analysis (36).…”