Polygenic scores for cardiovascular risk factors improve estimation of clinical outcomes in CCB treatment compared to pharmacogenetic variants alone
No Thumbnail Available
Authors
Türkmen, D.
Bowden, J.
Masoli, J. A. H.
Delgado, J.
Kuo, C. L.
Melzer, D.
Pilling, L. C.
Issue Date
2024-04-01
Type
Journal Article
Language
eng
Keywords
Humans , Calcium Channel Blockers/therapeutic use , Antihypertensive Agents/therapeutic use , *Hypertension/drug therapy , Pharmacogenomic Variants , *Cardiovascular Diseases/chemically induced , Risk Factors , *Heart Failure/drug therapy , Heart Disease Risk Factors , Lipoprotein(a)/therapeutic use
Alternative Title
Pharmacogenetic variants are associated with clinical outcomes during Calcium Channel Blocker (CCB) treatment, yet whether the effects are modified by genetically predicted clinical risk factors is unknown. We analyzed 32,000 UK Biobank participants treated with dihydropiridine CCBs (mean 5.9 years), including 23 pharmacogenetic variants, and calculated polygenic scores for systolic and diastolic blood pressures, body fat mass, and other patient characteristics. Outcomes included treatment discontinuation and heart failure. Pharmacogenetic variant rs10898815-A (NUMA1) increased discontinuation rates, highest in those with high polygenic scores for fat mass. The RYR3 variant rs877087 T-allele alone modestly increased heart failure risks versus non-carriers (HR:1.13, p = 0.02); in patients with high polygenic scores for fat mass, lean mass, and lipoprotein A, risks were substantially elevated (HR:1.55, p = 4 × 10(-5)). Incorporating polygenic scores for adiposity and lipoprotein A may improve risk estimates of key clinical outcomes in CCB treatment such as treatment discontinuation and heart failure, compared to pharmacogenetic variants alone.
Description
Citation
Türkmen D, Bowden J, Masoli JAH, Delgado J, Kuo CL, Melzer D, et al. Polygenic scores for cardiovascular risk factors improve estimation of clinical outcomes in CCB treatment compared to pharmacogenetic variants alone. The pharmacogenomics journal. 2024;24(3):12.
Publisher
Springer Nature
License
© 2024. The Author(s).
Journal
The pharmacogenomics journal