Abstract 13290: Minor Impact of Chromosome 9p21.3 Genetic Variation on Atherosclerosis Burden in Patients with Established Coronary Artery Disease
Background: Single nucleotide polymorphisms (SNPs) at 9p21.3 strongly predispose to coronary artery disease (CAD) but not to precipitation of myocardial infarction (MI). Whether 9p21.3 acts as an initiator versus an amplifier/accelerator of CAD is controversial. We studied the association of rs1333049 with CAD extent and severity.
Methods: Non-diabetic patients with angiographic CAD (i.e., ≥70% stenosis in ≥1 major vessel) enrolled from 1994-2003 in the Intermountain Heart Collaborative Study registry were evaluated for association of rs1333049 with Duke CAD Index, CAD lesion count, and number of diseased vessels (N1=405, Discovery set). An independent patient group (2003-2007) was studied for replication (N2=1,350, Validation set). Also, patients (n=593) without CAD (0-vessel disease: 0-69% stenosis) were compared to Discovery CAD patients.
Results: A weak association of rs1333049 (G>C) with mean CAD Index was found in Discovery patients: 43±16, 44±17, 47±18 for 0, 1, and 2 variant alleles, respectively (p-trend=0.06; adjusted [for age, sex, BMI, cardiac risk factors] p-trend=0.023). However, this association was not replicated in the larger Validation set: mean CAD Index: 42±16, 43±17, 44±18, respectively for 0, 1, and 2 variant alleles (adjusted p-trend=0.39). The lesion count was not different in the Discovery (2.7±2.1, 2.8±2.2, 3.1±2.3 for 0, 1, and 2 variant alleles; p-trend=0.16, adjusted p-trend=0.16) or the Validation set (adjusted p-trend=0.50). In Discovery patients, CC genotype frequency was modestly higher (p-trend=0.047) for 3-vessel (39%) than for 2- (30%) or 1-vessel CAD (25%). Similarly, in Validation patients, CC genotype was modestly higher in 3-vessel CAD (p-trend=0.016). In contrast, comparison of Discovery CAD with 0-vessel patients showed that rs1333049 markedly separated CAD from 0-vessel disease (p-trend=0.0003).
Conclusions: The 9p21.3 locus had a minor but consistent association with the number of diseased coronary vessels in non-diabetic CAD patients, but not with the CAD Index or the total lesion count. As expected, 9p21.3 strongly differentiated CAD from 0-vessel disease. These data support the concept that 9p21.3 influences plaque initiation in a vessel-dependent manner, but not CAD progression.
- © 2010 by American Heart Association, Inc.