Actionable pharmacogenetic variants in Hong Kong Chinese exome sequencing data and projected prescription impact in the Hong Kong population (e-poster)

Abstract

Introduction: Pharmacogenetics (PGx) encompasses the potential to improve therapeutic response and reduce adverse drug reaction in the era of precision medicine. However, Chinese PGx data is limited. To address this issue, we examined the spectrum of 133 actionable pharmacogenetic variants and rare deleterious variants in 108 pharmacogenes using an exome sequencing (ES) cohort. Methods: Secondary analysis of ES data was conducted to study pharmacogenetics in 1116 HK Chinese, which included 622 males and 494 females. The projected preemptive pharmacogenetic testing prescription impact was evaluated based on the patient prescription data between January 1, 2019 and December 31, 2019 in the HK public healthcare system, serving 7.5 million people and accounting for approximately 90% of all secondary and tertiary healthcare services provided. Results: Twenty-nine actionable pharmacogenetic variants/ alleles were identified in our cohort. Nearly all (99.6%) subjects carried at least one actionable pharmacogenetic variant, with a median of four variants, whereas 93.5% of subjects harbored at least one rare deleterious pharmacogenetic variant, with a median of two variants. The frequency of actionable genotypes was the highest in recipients of clopidogrel (57.21%), tacrolimus (43.38%), and warfarin (43.13%). Based on the prescription data of the public healthcare system in 2019, 13.4% of the HK population was prescribed with drugs with implicated actionable pharmacogenotypes in the HK population. 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 genotype. Conclusion: The results showed that secondary use of ES data is feasible for pharmacogenetic analysis, and preemptive pharmacogenetic testing has the potential to support prescription decisions in inpatient and specialist outpatient settings in the HK Chinese population. Acknowledgement: This study was supported by the Society for the Relief of Disabled Children, the Health and Medical Research Fund (HMRF), Li Ka Shing Donation Account: Enhanced New Staff Start-up Packages, the Children's Heart Foundation, and the Edward and Yolanda Wong Fund.