Beta-2 Polymorphisms and Beta Receptor Selectivity
| Status: | Completed |
|---|---|
| Conditions: | Cardiology |
| Therapuetic Areas: | Cardiology / Vascular Diseases |
| Healthy: | No |
| Age Range: | 18 - Any |
| Updated: | 4/21/2016 |
| Start Date: | January 2005 |
| End Date: | February 2007 |
The Effects of ß2 Polymorphisms on Beta Selectivity After ß-adrenergic Blockade in Patients With Heart Failure
We hypothesize that b2 adrenergic polymorphisms affect b-receptor selectivity in patients
with heart failure treated with either a b1-selective or a b-nonselective agent. b-2
polymorphisms may contribute to differing responses to drug treatment with beta-blockers in
heart failure. Characterizing these polymorphisms may help explain the variability in the
degree of "selectivity" of action of b-blockers at the b receptor, namely if their action is
specific for the b-1 or b-2 receptor. Part A was conducted at the University of Utah, and
all subjects completed study related activities. Part B (sub-study) consists of genotyping
of blood samples collected in part A, which will be completed at the University of
Wisconsin. Sub-study (samples and DNA isolation) or Part B entailed analyzing an extra 10 mL
of blood that was taken for DNA isolation. Genotyping (i.e. determination of genetic makeup)
of beta adrenergic polymorphisms utilized polymerase chain reaction followed by
pyrosequencing.
with heart failure treated with either a b1-selective or a b-nonselective agent. b-2
polymorphisms may contribute to differing responses to drug treatment with beta-blockers in
heart failure. Characterizing these polymorphisms may help explain the variability in the
degree of "selectivity" of action of b-blockers at the b receptor, namely if their action is
specific for the b-1 or b-2 receptor. Part A was conducted at the University of Utah, and
all subjects completed study related activities. Part B (sub-study) consists of genotyping
of blood samples collected in part A, which will be completed at the University of
Wisconsin. Sub-study (samples and DNA isolation) or Part B entailed analyzing an extra 10 mL
of blood that was taken for DNA isolation. Genotyping (i.e. determination of genetic makeup)
of beta adrenergic polymorphisms utilized polymerase chain reaction followed by
pyrosequencing.
Inclusion Criteria:
- systolic dysfunction with ejection fraction ≤40%
- symptomatic heart failure class 2-3
- >18 years of age
- optimal medical therapy of HF excluding the use of any beta-blockers within the
previous 30 days of the study
Exclusion Criteria:
- active myocarditis
- hemodynamically significant valvular heart disease
- hypertrophic cardiomyopathy
- contra-indications to beta-blockers
- concomitant use of beta-agonists
- beta-antagonist or anti-arrhythmics
- unstable angina
- myocardial infarction or bypass surgery within 3 months
- significant renal insufficiency [creatinine >2.5 mg/dL], liver disease, or anemia
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