CYP2C19 loss‐of‐function alleles are not associated with higher prevalence of gastrointestinal bleeds in those who have been prescribed antidepressants: Analysis in a British‐South Asian cohort
Year: 2023
Type: article
Study design: Observational Study
Abstract: AIMS: CYP2C19 is a hepatic enzyme involved in the metabolism of antidepressants associated with increased gastrointestinal bleed (GIB) risk. The aim of our study was to explore a possible association between loss-of-function CYP2C19 genotypes and GIB in South Asian ancestry participants prescribed antidepressants. METHODS: Genes & Health participants with a record in Barts Health NHS Trust (N 22 753) were studied using a cross-sectional approach. CYP2C19 diplotypes were assessed and metabolizer type inferred from consortia guidance. Fisher's exact test was used to compare the prevalence of GIB in different metabolizer categories. Multivariable regression was used to test for association between antidepressant prescriptions and GIB, and between CYP2C19 metabolizer state and GIB in the subcohort prescribed antidepressants. RESULTS: Antidepressants were frequently prescribed (47%, N = 10 612). A total of 864 participants (4%) had a GIB; 534 (62%) had been prescribed a CYP2C19 metabolized antidepressant. There was an independent association between antidepressant prescriptions and GIB events (odds ratio 1.8, confidence interval 1.5-2.0, P < 0.0001). There was no relationship between CYP2C19 inferred poor (P 0.56) or intermediate (P 0.53) metabolizer status and GIB in those prescribed an antidepressant in unadjusted analysis. A multivariable logistic regression model did not show an independent association between poor (P 0.54) or intermediate (P 0.62) CYP2C19 metabolizers and GIB in the subcohort prescribed antidepressants. CONCLUSIONS: CYP2C19 dependent antidepressants are associated with increased GIB prevalence. GIB appeared independent from CYP2C19 metabolizer genotype in individuals who had been prescribed antidepressants. Precision dosing based on CYP2C19 genetic information alone is unlikely to reduce GIB prevalence.
DOI: 10.1111/bcp.15762
Language: English
Subfield: Pharmacology
Domain: Life Sciences
Open Access status: hybrid
Estimated APC paid: $4,330
Funders: Bristol-Myers Squibb, Pfizer, GlaxoSmithKline, Alnylam Pharmaceuticals, Wellcome Trust, Broad Institute, Barts Charity, Maze Therapeutics, National Institute for Health and Care Research, King's College London, Public Health England, Novo Nordisk, Barts Health NHS Trust, Medical Research Council, NIHR Barts Biomedical Research Centre, Queen Mary University of London, Health Data Research UK
Awards: UK Infrastructure for Large-scale Clinical Genomics Research, East London Genes & Health: human knockouts in a population genomic medicine cohort of British-South Asians, Is exposure to toxic metals contributing to ethnic and social health inequalities in children and young adults in the UK?, G3364863151, G3417935152, UK Infrastructure for Large-scale Clinical Genomics Research, G4459349314, NIHR Senior Investigator Award, G5575271627, Genes & Health Longitudinal Population Study, NIHR Senior Investigator Award, Multimorbidity clusters, trajectories and genetic risk, in British south Asians, G829604083
OpenAlex ID: W4372319700