The clinical application of pharmacogenetics in understanding drug response
Abstract
Pharmacogenetics focuses on heritable factors that influence drug responses. For a given drug and patient, pharmacogenetics aims to optimise the intended therapeutic benefits, while minimising adverse drug reactions (ADR). Important pharmacogenes include those for drug metabolising enzymes CYP2D6, CYP2C19, and CYP2C9, and the transporter encoding SLCO1B1 and ABCG2 genes. The Understanding Adverse Drug Reactions Using Genomic Sequencing (UDRUGS) project was initiated in 2012 (Chua, 2015; Maggo et al., 2017). As a New Zealand biobank of clinical cases who have experienced a wide range of ADR or ineffectiveness towards drugs, UDRUGS provides a useful database for drug response phenotypes, contributing significantly to the samples used for analysis herein. The aim of this thesis was to study the application of pharmacogenetics in understanding two main drug response phenotypes: drug ineffectiveness and ADR, in the prescribing of antidepressants, statins, and proton-pump inhibitors (PPI). The role of pharmacogenetics in drug response phenotypes for antidepressants and statins was analysed using existing cohorts drawn from ongoing UDRUGS recruitment, while that of PPI, were new recruits. Heterogeneity in drug response is a well-recognised challenge in mental health, with high rates of ineffectiveness and incidence of ADR. A total of 52 cases were eligible, who experienced either ADR or ineffectiveness or both towards antidepressants. The allele and genotype-inferred phenotype…
How strong is the evidence?
Evidence Hub reads this as a cohort study, done in people. Its evidence level is 3 of 5 (Moderate · trial / cohort / secondary analysis). Trials without a large randomized design, cohorts and secondary analyses give moderate evidence. Reported size: 39 participants or records.
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