Background: It is uncertain whether the novel single nucleotide polymorphisms (SNPs) that have recently been associated with coronary artery disease (CAD) in genome-wide studies also influence carotid atheroma and stroke risk. The mechanisms of their association with CAD are unknown; relationships to other cardiovascular phenotypes may give mechanistic clues. Carotid artery intima-media thickness (CIMT) is a subclinical marker of atherosclerosis associated with stroke. We investigated association of reported CAD risk variants with CIMT, and with other intermediate phenotypes that may implicate causative pathways.
Methods: We studied 1425 members of 248 British Caucasian families ascertained through a hypertensive proband. We genotyped CAD risk SNPs on chromosomes 9 (rs1333049, rs7044859, rs496892, rs7865618), 6 (rs6922269) and 2 (rs2943634) using TaqMan. Merlin software was used for family-based association testing.
Results: No significant association was found between genotype at any SNP and CIMT in 846 individuals with acceptable measurements. Nor were SNPs significantly associated with blood pressure, obesity, cholesterol, CRP, interleukin-6, TNF-alpha, or leptin.
Conclusions: These novel CAD variants are not associated with CIMT and do not appear to mediate the risk of atherothrombosis through known risk factors.