Author + information
- Received April 28, 2014
- Revision received June 10, 2014
- Accepted June 12, 2014
- Published online December 1, 2014.
- Mathew R. Taylor, MD∗,
- Albert Y. Sun, MD†,
- Gordon Davis, MS‡,
- Mona Fiuzat, PharmD†,
- Stephen B. Liggett, MD§ and
- Michael R. Bristow, MD, PhD∗,‡∗ ()
- ∗Section of Pharmacogenetics, University of Colorado Cardiovascular Institute, Aurora, Colorado
- †Divisions of Cardiology and Clinical Pharmacology, Duke University Medical Center, Durham, North Carolina
- ‡ARCA biopharma, Westminster, Colorado
- §Center for Personalized Medicine and Genomics, University of South Florida, Morsani College of Medicine, Tampa, Florida
- ↵∗Reprint requests and correspondence:
Dr. Michael R. Bristow, Anschutz Medical Center, 12700 East 19th Avenue, P-15, Room 8003, Campus Box B-139, Aurora, Colorado 80045.
Because of its comparatively recent evolution, Homo sapiens exhibit relatively little within-species genomic diversity. However, because of genome size, a proportionately small amount of variation creates ample opportunities for both rare mutations that may cause disease as well as more common genetic variations that may be important in disease modification or pharmacogenetics. Primarily because of the East African origin of modern humans, individuals of African ancestry (AA) exhibit greater degrees of genetic diversity than more recently established populations, such as those of European ancestry (EA) or Asian ancestry. Those population effects extend to differences in frequency of common gene variants that may be important in heart failure natural history or therapy. For cell-signaling mechanisms important in heart failure, we review and present new data for genetic variation between AA and EA populations. Data indicate that: 1) neurohormonal signaling mechanisms frequently (16 of the 19 investigated polymorphisms) exhibit racial differences in the allele frequencies of variants comprising key constituents; 2) some of these differences in allele frequency may differentially affect the natural history of heart failure in AA compared with EA individuals; and 3) in many cases, these differences likely play a role in observed racial differences in drug or device response.
This study was supported by National Heart, Lung, and Blood Institute grants R01 HL7701 (Dr. Liggett) and 2R01 HL48013 (Dr. Bristow) and the Veterans’ Affairs Cooperative Studies Program. Dr. Taylor has received research grants and clinical trial support from Sanofi Therapeutics; and clinical trial support from Amicus Therapeutics and Array Biopharma. Dr. Sun is a consultant for St. Jude Medical; and has received research support from Medtronic Inc. Drs. Davis and Bristow are employees of and stock shareholders in ARCA biopharma, which is developing the beta-blocker/sympatholytic agent bucindolol. Dr. Liggett holds stock options in ARCA biopharma. Dr. Fiuzat has reported that she has no relationships relevant to the contents of this paper to disclose.
- Received April 28, 2014.
- Revision received June 10, 2014.
- Accepted June 12, 2014.
- American College of Cardiology Foundation
- Race and Genetic Variation
- Common Genetic Variation in Signaling Mechanisms Important in HF
- Does Common Genetic Variation Influence HF Natural History in Either AA or EA Populations?
- Genetic Variation and HF Therapy: Interaction of Race, Signaling Polymorphisms, and Therapeutic Responses