Abstract 1811: Novel Variants in Mitogen-Activated Protein Kinase (MAPK) Genes are Associated with Platelet Responsiveness to Aspirin

Abstract
Mitogen-activated protein kinases (MAPK), including p38 (MAPK11) and extracellular regulated kinases (ERK2 [MAPK1] and ERK3 [MAPK4]) mediate platelet aggregation after exposure to different agonists. However, the role of MAPKs and attendant genetic variations in modulating the response of platelets to aspirin (ASA) remains unknown. We measured platelet aggregation to epinephrine (epi) and collagen in platelet rich plasma at baseline and after 2 weeks of ASA (81 mg/day) in healthy white family members (N=1231) of probands (N=328) with premature coronary artery disease (CAD). Aspirin responsiveness was expressed as post-aspirin adjusted for pre-aspirin aggregation. Single nucleotide polymorphisms (SNPs), at 2– 4 kb density, in 3 MAPK genes (MAPK1, 11, and 4) were genotyped. Associations between SNPs and aspirin response phenotypes were examined using family-based variance components analysis (SAGE) with adjustment for sex, age, CAD risk factors, and plasma fibrinogen. Subjects had a mean age of 44.7 ± 13 years; 55% were women. A SNP in MAPK1 was significantly associated with epi-induced platelet aggregation (Table⇓). Two SNPs in linkage disequilibrium in MAPK4, were also significantly associated with this phenotype. Finally, a SNP in MAPK11 was significantly associated with collagen-induced platelet aggregation. These data suggest that common polymorphisms of 3 MAPK genes modulate platelet responsiveness to ASA.

SNPs in MAPK Genes Associated with Aspirin Responsiveness Phenotypes
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- Abstract 1811: Novel Variants in Mitogen-Activated Protein Kinase (MAPK) Genes are Associated with Platelet Responsiveness to AspirinBrian G Kral, Nauder Faraday, J. E Herrera-Galeano, Dhananjay Vaidya, Lisa R Yanek, Taryn F Moy, Diane M Becker and Lewis C BeckerCirculation. 2008;118:S_390, originally published January 18, 2016
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- Abstract 1811: Novel Variants in Mitogen-Activated Protein Kinase (MAPK) Genes are Associated with Platelet Responsiveness to AspirinBrian G Kral, Nauder Faraday, J. E Herrera-Galeano, Dhananjay Vaidya, Lisa R Yanek, Taryn F Moy, Diane M Becker and Lewis C BeckerCirculation. 2008;118:S_390, originally published January 18, 2016