Fellowship for Ryan Fischer: Aspirin-Related Gene Expression

Goals of the project: 1) Identify the prevalence of aspirin hyper-responders in the normal population. 2) Identify differences in gene expression between hyper-responders and nonna! reswnders, both before and after aspirin ingestion. Methods: Goal!. Up to 30 individuals will be screened by measuring bleeding times before aJ.'ldafter a single aspirin ingestion. Based on previous observations, this sample size will produce 3-4 aspirin hyperresponders. Up to 3 hyper-responders and 3 normal responders will be used in the microarray screening test (Affymetrix System). Goal 2: We plan to compare the phannacogenetic response to aspirin in 3 nonnal responders before and after aspirin ingestion using microarray technology to perform genome wide screening. RNA will be extracted from peripheral blood in three human volunteers, both before and 4 hours after aspirin ingestion (2 aspirin tablets - 365 mg per tablet). Differences in expressed m-RNA will be measured in individual samples using the beforeaspirin sample as the control Specimen. We also plan to perform genome wide screening in up to 3 hyperresponders before and after aspirin ingestion. The probe list generated from the normal. responders will be compared to the probe list from the hyper-responders. We also plan to compare the control samples of hyper - responders to those of nonnal responders in order to determine any differences present before aspirin administration. All donors will be the same gender.