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OIII‐B‐4
Author(s) -
Lobmeyer M. T.,
Terra S. G.,
Gong Y.,
Hamilton K. K.,
Pauly D. F.,
Patterson J. H.,
Adams K. F.,
Schofield R. S.,
Hill J. A.,
Aranda J. M.,
Johnson J. A.
Publication year - 2006
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1016/j.clpt.2005.12.113
Subject(s) - ejection fraction , metoprolol , heart failure , medicine , digoxin , cardiology , genotype , spironolactone , beta blocker , endocrinology , biology , gene , biochemistry
BACKGROUND Polymorphisms in the α 2c adrenergic receptor ( ADRA2C ) and the β 1 adrenergic receptor ( ADRB1 ) genes have been suggested to act synergistically in heart failure (HF) risk. We tested their association (and synergism) with β‐blocker (BB) response in HF. METHODS Left ventricular ejection fraction (EF) was determined by echocardiography at baseline and after 5–6 months of metoprolol CR/XL therapy in 54 patients with systolic HF. ADRB1 Arg389Gly and ADRA2C 322–325 Insertion/Deletion (Ins/Del) polymorphisms were determined by pyrosequencing. Linear regression modeling of end of study EF was done with patient age, race, genotypes, HF etiology, spironolactone, digoxin, and furosemide use and final metoprolol CR/XL dose considered in the model. EF response by genotype was compared by t‐tests and ANOVA. RESULTS Significant predictors of the end study EF were baseline EF, Del‐carrier status, Arg389Arg genotype and age. The combination of both genotypes (Arg389Arg & Del‐carrier) (Gp1) showed the greatest EF change. Adjusting for baseline EF and age, the end study EF of Gp1 was significantly different from the 3 other groups (overall p=0.0012) (table).Genotype combination baseline EF (%) end study EF (%) p value vs. Gp1Arg389Arg & Del‐carrier (Gp1) 22 ± 6 34 ± 15 ‐ Arg389Arg & Ins/Ins 24 ± 6 26 ± 7 0.0012 G389 carrier and Del‐carrier 24 ± 12 26 ± 15 0.0098 G389 carrier and Ins/Ins 20 ± 6 20 ± 6 0.0001CONCLUSIONS Polymorphisms in the ADRB1 and ADRA2C genes synergistically influence the left ventricular reverse remodeling response to β‐blockers in HF. Clinical Pharmacology & Therapeutics (2005) 79 , P31–P31; doi: 10.1016/j.clpt.2005.12.113