PAPI Profile
The Amish Pharmacogenomics of Anti-Platelet Intervention Study
| Website | http://medschool.umaryland.edu/Endocrinology/ |
|---|---|
| Principal Investigator | Alan R. Shuldiner, MD |
| Host Institution | University of Maryland School of Medicine |
| Grant Number | U01 GM074518-01 |
Abstract (July, 2005 Update)
Goals
The overall goal of this proposal is to dissect the genetic and molecular determinants of inter-individual variation in response to the anti-platelet agent's clopidogrel and aspirin, two medications used routinely for the treatment and prevention of cardiovascular disease (CVD).
Experimental Plans
We will build upon our large ongoing Heredity and Phenotype Intervention (HAPI) Heart Study, a study of 900 related Old Order Amish subjects who have been extensively characterized with respect to CVD and will soon have had a complete genome wide scan performed on their DNA. We propose to treat 600 of these subjects with clopidogrel and aspirin to obtain measures of platelet aggregation and function to quantitate drug response. We will:
- determine the frequency and heritability of clopidogrel response and the relationship between clopidogrel resistance and aspirin resistance;
- exhaustively define sequence variation and haplotype structure of 100 candidate genes and perform linkage and association analysis of SNPs/haplotypes with platelet function phenotypes;
- perform genome-wide linkage analysis to identify chromosome regions (and ultimately genes) linked to clopidogrel response.
The proposed studies will provide important insights into response to anti-platelet agents, which will have important implications for the prevention and treatment of CVD in millions of Americans.
PAPI Team
Principal Investigator
Email: ashuldin@medicine.umaryland.edu
Phone: (410) 706-1623
Investigator (consultant)
Email: Altshuler@molbio.mgh.harvard.edu
Phone: (617) 726-5940
Secretary or Assistant, for contact purposes: