Editors' ChoiceGenomics

Treatments for Atrial Fibrillation Get Personal

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Science Translational Medicine  08 Feb 2012:
Vol. 4, Issue 120, pp. 120ec19
DOI: 10.1126/scitranslmed.3003791

More than 2.3 million Americans suffer from a chronic condition known as atrial fibrillation (AF), which is characterized by chaotic electrical activity of the small heart chambers known as the atria. Such chaotic activity is transmitted to the larger ventricles, leading to fast heart rates, as well as an increased risk for stroke. For treatment, some choose to convert the individual out of AF by electrical shock or drugs, which is known as rhythm control. However, most physicians choose to slow heart rates through other commonly used drugs. This latter rate control strategy can be quite challenging. Thus, it is of great interest that Parvez et al. have now published data on genetic predictors of those patients most likely to respond to rate control therapy, such as beta blockers.

During a 36-month period, over 500 patients were prospectively enrolled in the Vanderbilt AF registry. Several clinical parameters and two common DNA variants in the β1-adrenergic receptor (ADRB1) were assessed to establish any predictive parameters for therapeutic success or failure. Although none of the clinical parameters were found to be useful in predicting response to rate-control drugs, carriers of a mutation in ADRB1 that resulted in an amino acid substitution of glycine for arginine at position 389 were found to be 40% more likely to respond to beta blockers, calcium channel blockers, and other commonly used rate-slowing agents. Mechanistically, this variant has been shown previously to be located in a region of ADRB1 known as the G protein–binding domain, with documented downstream effects that include reduced calcium influx and cell membrane depolarization. This connection supports how patients with the mutant receptor may respond to rate control drugs better than do those without the amino acid substitution.

Although additional mechanistic and clinical studies will need to be conducted to verify this tantalizing link between heart rate and drug treatment of AF, we can be sure that pharmacogenomics will become an important factor in guiding treatment of AF.

B. Parvez et al., A common β1-adrenergic receptor polymorphism predicts favorable response to rate-control therapy in atrial fibrillation. J. Am. Coll. Cardiol. 59, 49–56 (2012). [PubMed]

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