(Stroke. 2001;32:735.)
© 2001 American Heart Association, Inc.
Original Contributions |
A Common Variant of Endothelial Nitric Oxide Synthase (Glu298Asp) Is an Independent Risk Factor for Carotid Atherosclerosis
From the Department of Neurocardiology (G.L., C.B., A.A., M.M., G.F., F.P., C.V., B.T.), Neuromed Institute, Pozzilli (Isernia), Italy; Department of Internal Medicine (N. De L., G.I., B.T.), Federico II University, Napoli, Italy; Institute of Advanced Biomedical Technologies CNR (M.M.), Milan, Italy; and Department of Experimental Medicine and Pathology (G.L.), "La Sapienza" University, Rome, Italy.
Correspondence to Giuseppe Lembo, MD, PhD, IRCCS Neuromed, Località Camerelle, 86077 Pozzilli (IS), Italy. E-mail lembo{at}neuromed.it
Background and Purpose—Endothelium-derived NO is formed from L-arginine by endothelial NO synthase (eNOS) encoded by the NOS 3 gene on chromosome 7. Because several studies have indicated that NO plays a key role in the development of the atherosclerotic process, we investigated whether common variants in the eNOS gene are associated with an increased risk of plaque on carotid arteries.
Methods—We studied 375
subjects attending the hypertension center of our institution to be
screened for arterial hypertension. The examined subjects
were classified according to the presence of carotid plaques
(intima-media thickness 
1.5 mm), and 2 intronic (CA and 27-bp
repeats) polymorphisms and 1 exonic (Glu298Asp) polymorphism of
the eNOS gene were explored.
Results—Only the
Glu298Asp polymorphism of eNOS was associated with the presence of
carotid plaques (P<0.05). In
particular, there was an excess of homozygotes for the Asp298 variant
among subjects with carotid plaques, whereas the number of subjects who
had the Glu298 allele in exon 7 of the eNOS gene was equally
distributed in both study groups. Interestingly, the risk of having
carotid plaques was increased 
3 times in subjects who were
homozygotic for the Asp298 variant compared with subjects who were
homozygotic for the Glu298 variant and was independent of the other
common risk factors (age, blood pressure, and
smoking).
Conclusions—Homozygosity for Asp298, a common variant of the eNOS gene, is an independent risk factor for carotid atherosclerosis in this study population.
Key Words: atherosclerosis • carotid stenosis • genetics • nitric oxide • polymorphism
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