Posted on July 30, 2010
Gene dosage of 9p21 linked with coronary atheromatous burden severity
Anderson JL. J Am Coll Cardiol. 2010;56:487-489.
Dandona S. J Am Coll Cardiol. 2010;56:479-486.
Gene dosage of the risk variant 9p21 predicted coronary artery disease
burden in a new study appearing in the Journal of the American College of
Cardiology.
The Ottawa researchers performed this cross-sectional study on
nondiabetic patients with CAD defined by coronary angiography having at least
one epicardial
stenosis >50%. They enrolled 950 patients with early onset
CAD (age 56.1 ± 9.6 years) and an independent sample of 764 patients
with late onset CAD (age 70 ± 8 years) from the cardiac catheterization
laboratories at the University of Ottawa Heart Institute from April 15, 2006,
to Aug. 15, 2008. The patients were genotyped for the single nucleotide
polymorphism rs1333049 9p21 risk variant.
Researchers found that three-vessel disease had a direct association
with 9p21 gene dosage among younger CAD cases (P=4.26 ×
10-4), whereas one-vessel disease demonstrated an inverse
relationship with increasing gene
dosage (P=2.41 × 10-5). Gene dosage
also predicted three-vessel disease in a replication sample
(P=6.51 × 10-6). Further findings revealed that 9p21
did not associate with MI once stratified for disease severity.
“For the first time, we [have shown] that gene dosage of the 9p21
risk allele predicts CAD burden,” the researchers wrote. “Given its
ability to predict risk within a CAD population, genotyping 9p21 may be useful
not only in determining risk for development of disease but also for risk
stratification among patients with documented CAD.”
In an accompanying editorial, Jeffrey L. Anderson, MD, and
Benjamin D. Horne, PhD, MPH, both of the Intermountain Medical Center at
the University of Utah School of Medicine, said the researchers’
suggestion that the 9p21 marker may be useful in both primary and secondary
clinical risk assessment must be validated by prospective clinical studies.
“Nevertheless, this study importantly contributes to the growing
and stage-specific understanding of the role of genetics in CHD pathogenesis:
9p21 acts to facilitate initiation of coronary atherosclerosis, not to
precipitate MI,” they wrote.
