Genetic Determinants of Response to Beta Blockade

Genetic Determinants of Response to Beta Blockade

The overall goal of this project is to determine the genetic factors contributing to interindividual differences in response to beta-blockade.

The Aim is to define the contribution of genetic variation to the interindividual variability in response to β-blockade. The rationale for the study is as follows: Beta-blockers prevent the activation of β-ARs and thus form the cornerstone of treatment of pathological states such as congestive heart failure and coronary artery disease. Functional polymorphisms in cardiac beta-receptors have been shown to determine response to β-blocker therapy. A physiologic stimulus such as exercise causes sympathetic stimulation and activation of the cardiac β-ARs and genotypic differences in response to β-blockers are magnified under states of heightened sympathetic activity. Thus, in addition to measuring the response to β-blockers at rest, we will also determine the response to β-blockade after sub-maximal exercise on a supine bicycle ergometer. Genetic variations that may alter sensitivity to a beta blocker will be sought.

Inclusion Criteria:

• Subject must be willing to give written informed consent and be able to adhere to diet and study schedules.
• Subjects must be free of any clinically significant disease that requires a physician's care and/or would interfere with the study evaluations.
• Subjects must have a clinically acceptable physical examination and ECG.
• Laboratory tests (CBC, blood chemistries, and urinalysis) must be within clinically acceptable limits.

Exclusion Criteria:

• Any subject who has taken any prescription or over-the-counter drugs, other than oral contraception if female, within one week prior to study drug administration.
• Subjects who are presently, or were formerly, narcotic addicts or alcoholics.
• Active smokers.
• Subjects who have a clinically significant allergy/intolerance to atenolol.
• Females with a positive serum/urine pregnancy test at screening.
• Females who are nursing.
• Subjects with complete heart block/ any other significant cardiovascular disease.
• Subjects with a history of asthma symptoms or medication for it within last 10 years.
• Subjects who have a systolic blood pressure < 90 mm Hg or diastolic blood pressure < 50 mm Hg or heart rate < 50/min at the screening visit or on the baseline pre drug values on the study day.