title: Prospective Evaluation of Genetic Variation in Platelet Endothelial Aggregation Receptor 1 Reveals Aspirin-Dependent Effects on Platelet Aggregation Pathways.
abstract: Genetic variation in the platelet endothelial aggregation receptor 1 (PEAR1) gene, most notably rs12041331, is implicated in altered on-aspirin platelet aggregation and increased cardiovascular event risk. We prospectively tested the effects of aspirin administration at commonly prescribed doses (81, 162, and 324 mg/day) on agonist-induced platelet aggregation by rs12041331 genotype in 67 healthy individuals. Prior to aspirin administration, rs12041331 minor allele carriers had significantly reduced adenosine diphosphate (ADP)-induced platelet aggregation compared with noncarriers (P = 0.03) but was not associated with other platelet pathways. In contrast, rs12041331 was significantly associated with on-aspirin platelet aggregation when collagen and epinephrine were used to stimulate platelet aggregation (P < 0.05 for all associations), but not ADP. The influence of PEAR1 rs12041331 on platelet aggregation is pathway-specific and is altered by aspirin at therapeutic doses, but not in a dose-dependent manner. Additional studies are needed to determine the impact of PEAR1 on cardiovascular events in aspirin-treated patients.
authors.affiliation: Division of Endocrinology, Diabetes, and Nutrition, and Program for Personalized and Genomic Medicine, University of Maryland School of Medicine, Baltimore, Maryland, USA.
authors.forename: J D
authors.initials: JD
authors.lastname: Backman
authors.affiliation: Division of Endocrinology, Diabetes, and Nutrition, and Program for Personalized and Genomic Medicine, University of Maryland School of Medicine, Baltimore, Maryland, USA.
authors.forename: L M
authors.initials: LM
authors.lastname: Yerges-Armstrong
authors.affiliation: Division of Endocrinology, Diabetes, and Nutrition, and Program for Personalized and Genomic Medicine, University of Maryland School of Medicine, Baltimore, Maryland, USA.
authors.forename: R B
authors.initials: RB
authors.lastname: Horenstein
authors.affiliation: Division of Endocrinology, Diabetes, and Nutrition, and Program for Personalized and Genomic Medicine, University of Maryland School of Medicine, Baltimore, Maryland, USA.
authors.forename: S
authors.initials: S
authors.lastname: Newcomer
authors.affiliation: Division of Endocrinology, Diabetes, and Nutrition, and Program for Personalized and Genomic Medicine, University of Maryland School of Medicine, Baltimore, Maryland, USA.
authors.forename: S
authors.initials: S
authors.lastname: Shaub
authors.affiliation: Division of Endocrinology, Diabetes, and Nutrition, and Program for Personalized and Genomic Medicine, University of Maryland School of Medicine, Baltimore, Maryland, USA.
authors.forename: M
authors.initials: M
authors.lastname: Morrisey
authors.affiliation: Division of Endocrinology, Diabetes, and Nutrition, and Program for Personalized and Genomic Medicine, University of Maryland School of Medicine, Baltimore, Maryland, USA.
authors.forename: P
authors.initials: P
authors.lastname: Donnelly
authors.affiliation: Division of Endocrinology, Diabetes, and Nutrition, and Program for Personalized and Genomic Medicine, University of Maryland School of Medicine, Baltimore, Maryland, USA.
authors.forename: M
authors.initials: M
authors.lastname: Drolet
authors.affiliation: Division of Endocrinology, Diabetes, and Nutrition, and Program for Personalized and Genomic Medicine, University of Maryland School of Medicine, Baltimore, Maryland, USA.
authors.forename: K
authors.initials: K
authors.lastname: Tanner
authors.affiliation: Division of Endocrinology, Diabetes, and Nutrition, and Program for Personalized and Genomic Medicine, University of Maryland School of Medicine, Baltimore, Maryland, USA.
authors.forename: M A
authors.initials: MA
authors.lastname: Pavlovich
authors.affiliation: Division of Endocrinology, Diabetes, and Nutrition, and Program for Personalized and Genomic Medicine, University of Maryland School of Medicine, Baltimore, Maryland, USA.
authors.forename: J R
authors.initials: JR
authors.lastname: O'Connell
authors.affiliation: Division of Endocrinology, Diabetes, and Nutrition, and Program for Personalized and Genomic Medicine, University of Maryland School of Medicine, Baltimore, Maryland, USA.|Geriatrics Research and Education Clinical Center, Baltimore Veterans Administration Medical Center, Baltimore, Maryland, USA.
authors.forename: B D
authors.initials: BD
authors.lastname: Mitchell
authors.affiliation: Division of Endocrinology, Diabetes, and Nutrition, and Program for Personalized and Genomic Medicine, University of Maryland School of Medicine, Baltimore, Maryland, USA.
authors.forename: J P
authors.initials: JP
authors.lastname: Lewis
mesh_terms: D000244:Adenosine Diphosphate / Q000494:pharmacology; D000328:Adult; D000483:Alleles; D061365:Amish / Q000235:genetics; D001241:Aspirin / Q000494:pharmacology*; D015415:Biomarkers / Q000652:urine; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism; D003094:Collagen / Q000494:pharmacology; D004837:Epinephrine / Q000494:pharmacology; D005260:Female; D005838:Genotype; D064368:Healthy Volunteers; D006801:Humans; D008297:Male; D008875:Middle Aged; D010974:Platelet Aggregation / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D020641:Polymorphism, Single Nucleotide; D011446:Prospective Studies; D011956:Receptors, Cell Surface / Q000235:genetics*; D013929:Thromboxane B2 / Q000652:urine
chemical_list: D015415:Biomarkers; C502809:PEAR1 protein, human; D010975:Platelet Aggregation Inhibitors; D011956:Receptors, Cell Surface; D013929:Thromboxane B2; D000244:Adenosine Diphosphate; D003094:Collagen; D001241:Aspirin; D004837:Epinephrine