Abstract 20936: Determinants of PFA-100 Closure Time: A Genome-Wide Association Study
The Platelet Function Analyzer-100 (PFA-100, Dade-Behring) is an in vitro blood test of platelet function in the presence of shear stress and agonist stimulation. The aim of the current study was to identify genetic variants that determine collagen-epinephrine closure time (CEPI-CT) of the PFA-100in African Americans (AA) with replication in European Americans. Fasting blood samples were drawn from 836 healthy AA subjects and PFA-100 test was performed with prefabricated cartridges containing a combination of collagen and epinephrine as platelet agonists. Closure time was recorded in seconds. Genotyping was conducted with the Illumina 1M BeadChip array. Linear mixed effects models in SAS were used to test for association between each SNP and PFA-100 for all SNPs that met standard quality control criteria, after adjusting for age and sex. A replication sample consisted of 1244 healthy European Americans. Three SNPs were significantly associated with CEPI-CT at the GWAS Bonferroni threshold (p<10−8) in AA. Of the two SNPs (rs7562544 and rs4907312) that were in complete LD (r2=1) and were located 27kbp apart within the intronic regions of the NCAPH gene, rs7562544 was most strongly associated with CEPI-CT (p=9.2 × 10−9). The third SNP (rs2414721) was in the intergenic region on chromosome 15. All three SNPs were also significantly associated with CEPI-CT in European Americans (p<0.05). The minor allele of rs7562544 and major allele of rs2414721 were associated with decreased CEPI-CT in both races (table). The NACPH gene codes for a protein involved in chromatin condensation and is known to be expressed in platelet precursor megakaryocytes. In this first reported GWAS of PFA-100 in AA, we have identified three genetic variants and replicated these variants in a sample of European Americans. These findings may enhance our understanding of platelet biology and are likely to have clinical hemostasis implications.
- © 2010 by American Heart Association, Inc.