Polymorphisms of the β 2 -Adrenergic Receptor Determine Exercise Capacity in Patients With Heart Failure
| Autor: | Balkrishna Singh, Lynne E. Wagoner, William T. Abraham, Thomas C. Chenier, Damodhar P. Suresh, Paul W. Zengel, Laura L. Craft, Nancy McGuire, Stephen B. Liggett, Gerald W. Dorn |
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| Rok vydání: | 2000 |
| Předmět: |
Male
medicine.medical_specialty Heart disease Physiology Cardiac index Physical exercise Internal medicine medicine Humans Genetic Predisposition to Disease In patient Exercise Alleles Heart Failure Polymorphism Genetic business.industry Stroke volume Middle Aged medicine.disease medicine.anatomical_structure Endocrinology Relative risk Heart failure Vascular resistance Cardiology Female Receptors Adrenergic beta-2 Cardiology and Cardiovascular Medicine business |
| Zdroj: | Circulation Research. 86:834-840 |
| ISSN: | 1524-4571 0009-7330 |
| DOI: | 10.1161/01.res.86.8.834 |
| Popis: | Abstract —The β 2 -adrenergic receptor (β 2 AR) exists in multiple polymorphic forms with different characteristics. Their relevance to heart failure (HF) physiology is unknown. Cardiopulmonary exercise testing was performed on 232 compensated HF patients with a defined β 2 AR genotype. Patients with the uncommon Ile164 polymorphism had a lower peak V̇ o 2 (15.0±0.9 mL · kg −1 · min −1 ) than did patients with Thr164 (17.9±0.9 mL · kg −1 · min −1 , P o 2 was also lower in patients with Ile164 (62.3±4.5% versus 71.5±5.1%, P =0.045). The relative risk of a patient having a V̇ o 2 ≤14 mL · kg −1 · min −1 who had Ile164 was 8.0 ( P =0.009). Catheterization-based invasive exercise testing revealed depressed changes in the exercise-induced cardiac index, systemic vascular resistance, stroke volume, and V̇ o 2 in patients with Ile164. The polymorphisms at position 16 also impacted exercise capacity: peak V̇ o 2 for Arg16 versus Gly16 was 17.0±0.8 versus 15.6±0.5 mL · kg −1 · min −1 , respectively ( P =0.03). Because the polymorphisms at loci 16 and 27 can occur together, 4 homozygous combinations exist. Patients with Arg16/Glu27 had the highest percentage achieved of predicted peak V̇ o 2 (75.7±6.4%), whereas those with Gly16/Gln27 had the lowest (55.3±2.8%, P =0.0032). The above findings were not confounded by baseline clinical characteristics, including β-blocker usage. We conclude that the β 2 AR polymorphisms Ile164, Gly16, and the combination of Gly16 and Gln27 are associated with depressed exercise performance in HF and represent a genetically determined factor in the pathophysiology of HF. |
| Databáze: | OpenAIRE |
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