Determination of the Genetic Contribution to Glycemic Control and CAD Outcomes in Patients with DM2 and CAD

Sharon Cresci, M.D.

Project Overview:
Diabetes mellitus (DM) currently affects more than 220 million people worldwide and its prevalence is increasing. Among persons with DM, complications of accelerated atherosclerosis, particularly acute coronary events, are the principal cause of death. To date, few studies have examined the hypothesis that genetic variation may account for variable responses to treatment and variable clinical outcomes among patients with DM and coronary artery disease (CAD).

The Bypass Angioplasty Revascularization Investigation 2 Diabetes (BARI 2D) is a multicenter trial examining the effects of different approaches to treatment of CAD and DM on long-term outcomes in patients with type 2 DM. This study will use genetic samples from BARI 2D trial participants to examine the PPARalpha gene to determine if specific gene sequence differences can predict poor outcomes and better or worse patient responses to certain treatments for DM or CVD.

Progress Report: 
A year ago, 363 Brazilian BARI 2D genetic samples became available for genotyping. In the first year of funding, most of these samples were processed and genotyped. A manuscript reporting the PPAR pathway gene variant associated with extent of CAD in the BARI 2D study was accepted by the American Heart Association’s journal, Circulation, for publication.

In the project’s second year, novel analyses will be used to determine PPAR pathway gene variants that show an association with clinical cardiovascular and diabetic outcomes, and to identify gene variants that have a significant pharmacogenomic interaction between diabetes medications and outcomes.