Novel genetic variants linked to coronary artery disease by genome-wide association are not associated with carotid artery intima-media thickness or intermediate risk phenotypes.
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.
Cunnington
M S
MS
Mayosi
B M
BM
Hall
D H
DH
Avery
P J
PJ
Farrall
M
M
Vickers
M A
MA
Watkins
H
H
Keavney
B
B
D000328:Adult; D000368:Aged; D002339:Carotid Arteries / Q000473:pathology*; D003324:Coronary Artery Disease / Q000235:genetics*; D005260:Female; D014644:Genetic Variation; D055106:Genome-Wide Association Study; D006801:Humans; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D012306:Risk; D017539:Tunica Intima / Q000473:pathology*; D017540:Tunica Media / Q000473:pathology*