title: Race, common genetic variation, and therapeutic response disparities in heart failure.
abstract: 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.
authors.affiliation: Section of Pharmacogenetics, University of Colorado Cardiovascular Institute, Aurora, Colorado.
authors.forename: Mathew R
authors.initials: MR
authors.lastname: Taylor
authors.affiliation: Divisions of Cardiology and Clinical Pharmacology, Duke University Medical Center, Durham, North Carolina.
authors.forename: Albert Y
authors.initials: AY
authors.lastname: Sun
authors.affiliation: ARCA biopharma, Westminster, Colorado.
authors.forename: Gordon
authors.initials: G
authors.lastname: Davis
authors.affiliation: Divisions of Cardiology and Clinical Pharmacology, Duke University Medical Center, Durham, North Carolina.
authors.forename: Mona
authors.initials: M
authors.lastname: Fiuzat
authors.affiliation: Center for Personalized Medicine and Genomics, University of South Florida, Morsani College of Medicine, Tampa, Florida.
authors.forename: Stephen B
authors.initials: SB
authors.lastname: Liggett
authors.affiliation: Section of Pharmacogenetics, University of Colorado Cardiovascular Institute, Aurora, Colorado; ARCA biopharma, Westminster, Colorado. Electronic address: michael.bristow@ucdenver.edu.
authors.forename: Michael R
authors.initials: MR
authors.lastname: Bristow
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000627:therapeutic use; D005787:Gene Frequency / Q000235:genetics; D014644:Genetic Variation / Q000235:genetics*; D005838:Genotype; D006333:Heart Failure / Q000235:genetics* / Q000401:mortality / Q000628:therapy; D006801:Humans; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D044469:Racial Groups / Q000235:genetics*; D011941:Receptors, Adrenergic / Q000235:genetics; D015398:Signal Transduction / Q000235:genetics; D016896:Treatment Outcome
chemical_list: D000319:Adrenergic beta-Antagonists; D011941:Receptors, Adrenergic
keywords: genetic polymorphisms; heart failure; pharmacogenetics; racial ancestry