The chromosome 9p21 risk locus is associated with angiographic severity and progression of coronary artery disease.
OBJECTIVE
we tested the hypothesis that the 9p21 risk locus promotes atherosclerosis by examining the association between rs10757278 and coronary artery disease (CAD) severity and progression determined by semi-quantitative angiographic scores.


RESULTS
the rs10757278 single nucleotide polymorphism (SNP) was genotyped as the marker for the 9p21 locus in 2334 Caucasian patients undergoing cardiac catheterization (mean age 63, male 67%). Angiographic CAD was assessed using two semi-quantitative scoring systems with one estimating severity (Gensini) and the other extent (Sullivan). A subset of 308 patients who underwent two or more coronary angiograms at least 6 months apart were examined for net change in Gensini and Sullivan scores over time to determine the rate of CAD progression by genotype and were further classified as 'progressors' or 'non-progressors' based on absolute change per year in angiographic severity score. We replicated the association between the rs10757278 SNP and myocardial infarction and binary (presence/absence) angiographic classifications of CAD. Furthermore, we observed a significant additive association with this SNP, and both severity and extent of CAD using angiographic scores, after adjustment for age, gender, body mass index, traditional cardiovascular risk factors, myocardial infarction, and statin use (Gensini P = 0.016, Sullivan P = 0.005). In addition, there was a significant linear association with CAD progression before and after adjustment for covariates (Gensini P = 0.023, Sullivan P = 0.003) with homozygotes for the risk variant having three-fold greater odds of CAD progression compared with the referent group.


CONCLUSIONS
the 9p21 risk locus is associated with angiographically defined severity, extent, and progression of CAD, suggesting a role for this locus in influencing atherosclerosis and its progression.
Patel
Riyaz S
RS
Division of Cardiology, Emory University School of Medicine, Emory University Hospital, 1364 Clifton Road, 4th Floor, Suite D403C, Atlanta, GA 30322, USA.
Su
Shaoyong
S
Neeland
Ian J
IJ
Ahuja
Ayushi
A
Veledar
Emir
E
Zhao
Jinying
J
Helgadottir
Anna
A
Holm
Hilma
H
Gulcher
Jeffrey R
JR
Stefansson
Kari
K
Waddy
Salina
S
Vaccarino
Viola
V
Zafari
A Maziar
AM
Quyyumi
Arshed A
AA
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002899:Chromosomes, Human, Pair 9 / Q000235:genetics*; D017023:Coronary Angiography; D003324:Coronary Artery Disease / Q000000981:diagnostic imaging / Q000235:genetics*; D018450:Disease Progression; D005260:Female; D005819:Genetic Markers / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000235:genetics; D005838:Genotype; D006720:Homozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000000981:diagnostic imaging / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D012307:Risk Factors; D055815:Young Adult
D005819:Genetic Markers