Influence of eNOS gene polymorphisms on carotid atherosclerosis.
BACKGROUND
Nitric oxide (NO) is an endothelium-derived relaxing factor which plays a role in atherogenetic events. Polymorphisms in the endothelial NO synthase gene (eNOS) influences the functional activity of the enzyme and affect the susceptibility to atherogenesis. In this study we determined whether T-786C, G894T and 4a/4b eNOS genetic variants may increase the susceptibility to carotid atherosclerosis.


METHODS
The study groups included 304 consecutive patients with severe carotid stenosis (>/=70%) and 544 control subjects. The eNOS polymorphisms were analysed by molecular biology techniques.


RESULTS
The genotype distribution and allele frequency of eNOS 4a/4b, but not T-786C and G894T, polymorphism was significantly different between patients and controls. Using logistic regression with adjustment for other risk factors, the 4a allele and the combined genotype 4a4a+4a4b/894TT+GT and -786CC+TC/894TT+GT were associated with carotid stenosis (OR=1.5, p=0.02; OR=1.8, p=0.01; OR=1.5, p=0.04, respectively). In a subset of patients (30 of 304) with no traditional risk factors for atherosclerosis, a relatively high incidence of the 4a allele and 4a4a+4a4b/-786CC+TC combined genotype was noted.


CONCLUSIONS
Our findings suggest that the 4a allele and the eNOS combined genotypes are independent predisposing factors to carotid atherosclerosis.
Fatini
C
C
Department of Clinical and Surgical Critical Care, Section of Clinical Medicine, Thrombosis Centre, University of Florence, Florence, Italy.
Sofi
F
F
Gensini
F
F
Sticchi
E
E
Lari
B
B
Pratesi
G
G
Pulli
R
R
Dorigo
W
W
Pratesi
C
C
Gensini
G F
GF
Abbate
R
R
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002340:Carotid Artery Diseases / Q000201:enzymology / Q000235:genetics*; D016022:Case-Control Studies; D016009:Chi-Square Distribution; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D019001:Nitric Oxide Synthase / Q000235:genetics*; D011110:Polymorphism, Genetic
D019001:Nitric Oxide Synthase