Case Number 108017 - Personalized Medicine - A Test for Individualized Cardiovascular Disease Treatment Protocols Based on Beta-1 Adrenergic Receptor Haplotype

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Description:  ß-adrenergic receptors (ß-AR's) a class of G protein-coupled receptors that are targets of the catecholamines, especially noradrenaline (norepinephrine) and adrenaline (epinephrine). ß receptors have the subtypes ß1, ß2 and ß3. All three are linked to Gs proteins, which in turn are linked to adenylate cyclase. Agonist binding to these receptors therefore causes a rise in the intracellular concentration of the second messenger cAMP.

ß subtype1-adrenergic receptors (ß1-AR's)  are expressed on a number of cell types, including cardiomyocytes, vascular smooth muscle, epithelium, renal juxtaglomerular, and adipocytes. These receptors are targets for agonists in the acute treatment of decompensated heart failure, while ß1-AR antagonists are utilized in the treatment of cardiovascular diseases such as chronic heart failure, ischemic heart disease, cardiac arrhythmias, and hypertension. However, the response to ß1-AR agonists or antagonists appears to be highly variable between individuals, which is not readily explained by clinical status or demographic characteristics. Furthermore, the inventor has previously shown that the expression of ß1-AR, and the responsiveness to stimulation, can differ substantially between healthy individuals. Such variability between individuals suggests that the receptor may be polymorphic in the population, giving rise to altered expression as well as altered physiologic or pharmacologic responsiveness.

Dr. Stephen Liggett at the University of Cincinnati has invented a method for determining whether a treatment protocol for a human patient who is suffering from heart failure, ischemic heart disease, cardiac arrhythmias, or hypertension would include the administration of a beta blocker. The method also involves identifying locations of any polymorphisms in the ß1-AR sequence from the patient's biological sample, assigning a haplotype to the ß1-AR sequence based on the locations identified, and determining whether the treatment protocol includes administration of a beta blocker to the patient based on the haplotype assigned.

The invention offers the following advantages:

A patent for this technology is pending. The published patent application can be found here