دورية أكاديمية
أعرض في EDS

Polygenic scores for cardiovascular risk factors improve estimation of clinical outcomes in CCB treatment compared to pharmacogenetic variants alone.

التفاصيل البيبلوغرافية
العنوان: Polygenic scores for cardiovascular risk factors improve estimation of clinical outcomes in CCB treatment compared to pharmacogenetic variants alone.
المؤلفون: Türkmen D; Epidemiology & Public Health Group, Department of Clinical & Biomedical Science, Faculty of Health & Life Sciences, University of Exeter, Exeter, UK., Bowden J; Exeter Diabetes Group (ExCEED), Department of Clinical & Biomedical Science, Faculty of Health & Life Sciences, University of Exeter, Exeter, UK.; Department of Genetics, Novo Nordisk Research Centre Oxford, Innovation Building, Old Road Campus, Roosevelt Drive, Oxford, UK., Masoli JAH; Epidemiology & Public Health Group, Department of Clinical & Biomedical Science, Faculty of Health & Life Sciences, University of Exeter, Exeter, UK.; Department of Healthcare for Older People, Royal Devon University Healthcare NHS Foundation Trust, Barrack Road, Exeter, UK., Delgado J; Epidemiology & Public Health Group, Department of Clinical & Biomedical Science, Faculty of Health & Life Sciences, University of Exeter, Exeter, UK., Kuo CL; UConn Center on Aging, University of Connecticut, Farmington, CT, USA.; Connecticut Convergence Institute for Translation in Regenerative Engineering, University of Connecticut, Storrs, CT, USA., Melzer D; Epidemiology & Public Health Group, Department of Clinical & Biomedical Science, Faculty of Health & Life Sciences, University of Exeter, Exeter, UK., Pilling LC; Epidemiology & Public Health Group, Department of Clinical & Biomedical Science, Faculty of Health & Life Sciences, University of Exeter, Exeter, UK. L.Pilling@exeter.ac.uk.
المصدر: The pharmacogenomics journal [Pharmacogenomics J] 2024 Apr 17; Vol. 24 (3), pp. 12. Date of Electronic Publication: 2024 Apr 17.
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: Nature Pub. Group Country of Publication: United States NLM ID: 101083949 Publication Model: Electronic Cited Medium: Internet ISSN: 1473-1150 (Electronic) Linking ISSN: 1470269X NLM ISO Abbreviation: Pharmacogenomics J Subsets: MEDLINE
أسماء مطبوعة: Original Publication: Avenet, NJ : Nature Pub. Group, c2001-
مواضيع طبية MeSH: Hypertension*/drug therapy , Cardiovascular Diseases*/chemically induced , Heart Failure*/drug therapy, Humans ; Calcium Channel Blockers/therapeutic use ; Antihypertensive Agents/therapeutic use ; Pharmacogenomic Variants ; Risk Factors ; Heart Disease Risk Factors ; Lipoprotein(a)/therapeutic use
مستخلص: 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.
(© 2024. The Author(s).)
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معلومات مُعتمدة: MR/X011372/1 RCUK | Medical Research Council (MRC); MR/X011372/1 RCUK | Medical Research Council (MRC); MR/X011372/1 RCUK | Medical Research Council (MRC); NIHR301445 DH | National Institute for Health Research (NIHR); grant: 338 (AS-JF-16b-007) Alzheimer's Society
المشرفين على المادة: 0 (Calcium Channel Blockers)
0 (Antihypertensive Agents)
0 (Lipoprotein(a))
تواريخ الأحداث: Date Created: 20240417 Date Completed: 20240419 Latest Revision: 20240615
رمز التحديث: 20240615
مُعرف محوري في PubMed: PMC11023935
DOI: 10.1038/s41397-024-00333-2
PMID: 38632276
قاعدة البيانات: MEDLINE
الوصف
تدمد:1473-1150
DOI:10.1038/s41397-024-00333-2