Heart Care Info - Heart Disease Prevention & Treatment

Peroxisome Proliferator-Activated Receptor Pathway Gene Polymorphism Associated With Extent of Coronary Artery Disease in Patients With Type 2 Diabetes in the ...

S Cresci, J Wu, MA Province, JA Spertus... - Circulation, 2011 - Am Heart Assoc BackgroundCoronary artery disease (CAD) is the major cause of death in patients with type 2 diabetes mellitus. Although demographic and clinical factors associated with extent of CAD in patients with diabetes mellitus have been described, genetic factors have not. We ...

Methods and Results—We genotyped 1043 patients (702 white, 175 blacks) from the Bypass Angioplasty Revascularization Investigation 2 Diabetes (BARI 2D) genetic cohort for 3351 variants in 223 PPAR pathway genes using a custom targeted-genotyping array. Angiographic end points were determined by a core laboratory. In whites, a single variant (rs1503298) in TLL1 was significantly (P=5.5×10−6) associated with extent of CAD, defined as number of lesions with percent diameter stenosis ≥20%, after stringent Bonferroni correction for all 3351 single nucleotide polymorphisms. This association was validated in the diabetic subgroups of 2 independent cohorts, the Translational Research Investigating Underlying Disparities in Acute Myocardial Infarction Patients' Health Status (TRIUMPH) post–myocardial infarction registry and the prospective Family Heart Study (FHS) of individuals at risk for CAD. TLL1rs1503298 was also significantly associated with extent of severe CAD (≥70% diameter stenosis; P=3.7×10−2) and myocardial jeopardy index (P=8.7×10−4). In general linear regression modeling, TLL1rs1503298 explained more variance of extent of CAD than the previously determined clinical factors.