This proposal describes a 5-year training program to prepare Dr. H. Jacqueline Suk for an academic career in cardiovascular epidemiology, with a special emphasis in genetic epidemiology. Dr. Suk received her MD degree from Harvard Medical School in 1997 and completed medical residency training at Columbia-Presbyterian Hospital in 2000. She expects to complete a clinical and research cardiology fellowship from Brigham & Women's Hospital in 2004, in addition to an MPH degree from the Harvard School of Public Health in 2003. Paul M. Ridker, MD, MPH, and Robert Zee, PhD, will mentor the principal investigator's scientific development. Dr. Ridker is Director of the Center for Cardiovascular Disease Prevention, and Assistant Professor of Medicine. Dr. Ridker has trained numerous investigators in the field of cardiovascular disease prevention, has numerous NIH-funded R01 grants, as well as an extensive publication record. Dr. Zee has extensive experience in running a state-of-the-art, high throughput genetics facility, and has an impressive record of high-quality publications in this field. Dr. Suk's research will build on her preliminary results, which identify a strong association between two single nucleotide polymorphisms (SNPs) in the C-reactive protein (CRP) gene and CRP levels in men and women. She will build haplotypes of SNPs within the CRP gene and assess their associations with CRP levels. She will then genotype SNPs within several neighboring genes of inflammatory proteins, building haplotypes across both the CRP gene and these inflammatory genes. These haplotypes will then be assessed for their relationship to CRP levels, a potent marker and arguably mediator of inflammation. A strength of this proposal is that the investigations are being performed on an already completed study, the Pravastatin Inflammation/CRP Evaluation (PRINCE) trial of 2743 participants, all of whom have already had full CRP and lipid panel evaluations and have provided consent for genetic study. Dr. Suk will investigate three main hypotheses: 1) haplotypes of polymorphisms within the CRP gene affect CRP levels, 2) haplotypes of polymorphisms of inflammatory proteins around the CRP gene affects CRP levels, and 3) interactions between such haplotypes and """"""""environmental"""""""" factors such as medical therapy and smoking affect CRP levels and change in CRP levels over time. The confirmatory phase will consist of validation of these relationships in other large available clinical cohorts in the Division of Preventive Medicine. The Division of Preventive Medicine at Brigham & Women's Hospital provides an ideal setting for training physician-scientists. At the end of the proposed research program, Dr. Suk will have attained advanced skills in genetics and epidemiology which can then be applied to independent research in genetic epidemiology and cardiovascular disease.
