{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"omics_type":["Unknown"],"volume":["18(5)"],"submitter":["Luzum JA"],"pubmed_abstract":["Previous pharmacogenetic findings for beta-blocker pharmacodynamic candidate genes (ADRB1, ADRB2, ADRA2C, GRK4, and GRK5) have been inconsistent. Therefore, the purpose of this study was to determine whether interactions of pharmacodynamic variants with beta-blocker exposure significantly associated with survival in patients with heart failure with reduced ejection (HFrEF). The 893 patients were 51% self-reported African American and 49% self-reported White race, 36% female, and 240 died (27%) over a median follow-up of 2.8 years. The primary outcome was all-cause mortality. Using Cox proportional hazards models with time-varying beta-blocker exposure and adjusted for clinical risk factors and ancestry, interactions of ADRB1 Arg389Gly, ADRB1 Ser49-Arg389Gly haplotype, ADRA2C Del<sub>322-325</sub>, and GRK4 Ala486Val with beta-blocker exposure were significant before correction for multiple comparisons (p < 0.1), but only GRK4 Ala486Val remained significant in African Americans after correction for multiple comparisons using the adaptive Hochberg method (p = 0.022). Beta-blocker exposure only associated with a significant reduction in the risk of mortality in the African American HFrEF patients with the GRK4 Ala486/Ala486 genotype (HR = 0.44; 95% CI = 0.20-0.96; p = 0.04). In conclusion, the interaction of GRK4 Ala486Val with beta-blocker exposure significantly associated with survival in African American HFrEF patients. Larger sample sizes or meta-analyses are needed to have more statistical power to better assess beta-blocker pharmacogenetic interactions for ADRB1 Arg389Gly, ADRB1 Ser49-Arg389Gly haplotype, and ADRA2C Del<sub>322-325</sub> in the future."],"journal":["Clinical and translational science"],"pagination":["e70239"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC12031879"],"repository":["biostudies-literature"],"pubmed_title":["The Beta-Blocker Pharmacogenetic Puzzle: More Pieces of Evidence for Pharmacodynamic Candidate Variants."],"pmcid":["PMC12031879"],"pubmed_authors":["She R","Lopez-Medina AI","Littleton SDR","Lanfear DE","Luzum JA","Liu B"],"additional_accession":[]},"is_claimable":false,"name":"The Beta-Blocker Pharmacogenetic Puzzle: More Pieces of Evidence for Pharmacodynamic Candidate Variants.","description":"Previous pharmacogenetic findings for beta-blocker pharmacodynamic candidate genes (ADRB1, ADRB2, ADRA2C, GRK4, and GRK5) have been inconsistent. Therefore, the purpose of this study was to determine whether interactions of pharmacodynamic variants with beta-blocker exposure significantly associated with survival in patients with heart failure with reduced ejection (HFrEF). The 893 patients were 51% self-reported African American and 49% self-reported White race, 36% female, and 240 died (27%) over a median follow-up of 2.8 years. The primary outcome was all-cause mortality. Using Cox proportional hazards models with time-varying beta-blocker exposure and adjusted for clinical risk factors and ancestry, interactions of ADRB1 Arg389Gly, ADRB1 Ser49-Arg389Gly haplotype, ADRA2C Del<sub>322-325</sub>, and GRK4 Ala486Val with beta-blocker exposure were significant before correction for multiple comparisons (p < 0.1), but only GRK4 Ala486Val remained significant in African Americans after correction for multiple comparisons using the adaptive Hochberg method (p = 0.022). Beta-blocker exposure only associated with a significant reduction in the risk of mortality in the African American HFrEF patients with the GRK4 Ala486/Ala486 genotype (HR = 0.44; 95% CI = 0.20-0.96; p = 0.04). In conclusion, the interaction of GRK4 Ala486Val with beta-blocker exposure significantly associated with survival in African American HFrEF patients. Larger sample sizes or meta-analyses are needed to have more statistical power to better assess beta-blocker pharmacogenetic interactions for ADRB1 Arg389Gly, ADRB1 Ser49-Arg389Gly haplotype, and ADRA2C Del<sub>322-325</sub> in the future.","dates":{"release":"2025-01-01T00:00:00Z","publication":"2025 May","modification":"2026-06-02T04:12:34.942Z","creation":"2025-07-07T03:08:19.156Z"},"accession":"S-EPMC12031879","cross_references":{"pubmed":["40285373"],"doi":["10.1111/cts.70239"]}}