| dc.description.abstract | Background: Personalized prescribing with genetic information can decrease adverse drug reactions (ADRs) and increase therapeutic efficacy. Health inequality is a well acknowledged problem, and British south-Asians suffer from disproportionate multimorbidity contributing to polypharmacy and are under-represented in research. Aims: To characterise the prevalence of well validated pharmacogene variants in the Genes & Health (G&H) British-Bangladeshi and British-Pakistani population, and link these with medication exposure and real-world clinical outcome events to assess safety and efficacy outcomes. Furthermore, to engage this community in qualitative research around pharmacogenomics implementation and research acceptability. Methods: The G&H study cohort (N = 44,396) was used to associate validated polymorphisms in two genes central to drug metabolism (CYP2C19 and SLCO1B1), and Factor V Leiden (FVL), a known prothrombotic mutation, with therapeutic efficacy and adverse drug reactions, controlling for confounders as co-variates in multivariable logistic regression analyses. Thematic analysis of focus groups was undertaken to characterise participants attitudes toward pharmacogenomics. Results: The G&H cohort have a high prevalence of loss-of-function polymorphisms in the pharmacokinetic CYP2C19 gene. In clopidogrel exposed participants, poor metabolizer state was associated with therapeutic failure in participants who had experienced a myocardial infarction. Presence of the SLCO1B*5 allele, a genetic proxy for increased statin exposure, was associated with lower prevalence of young onset cataracts in participants exposed to statins. The absolute risk of thrombosis associated with FVL and oestrogen use was non trivial in the context of multimorbidity. Public acceptability for pharmacogenomics implementation and research hinge on trust and trust is linked with medication compliance. Pharmacogenomic testing may increase the likelihood of compliance on top of a direct gene-drug affect. Conclusions: Personalised prescribing may improve clinical care for ancestry cohorts underrepresented in trial data. Pharmacogenes are useful tools to interrogate observational data for purported links between medications and adverse drug events. | en_US |
