eNOS G894T polymorphism as a mild predisposing factor for abdominal aortic aneurysm.
OBJECTIVE
Abdominal aortic aneurysm (AAA) represents a chronic degenerative condition associated with atherosclerosis. Actually, data from experimental and clinical studies suggest that nitric oxide (NO) is a modulator in maintaining endothelial function and antithrombotic intravascular environment. Reduced vascular NO generation in subjects carrying the rare variants of the eNOS gene might predispose to AAA. No information is available about the influence of the eNOS gene T-786C, G894T, and 4a/4b polymorphisms in the susceptibility to the disease.


METHODS
In this study, we evaluated the role of these polymorphisms in the predisposition to AAA and their influence in hypertensive and normotensive patients. We studied 250 consecutive patients with AAA referred to the Unit of Vascular Surgery of the University of Florence compared with 250 truly healthy subjects with a negative history of vascular diseases. All subjects, patients, and controls, underwent duplex scanning examination, and to assess the presence of other atherosclerotic localizations, all patients underwent clinical and instrumental examinations.


RESULTS
A significant difference in genotype distribution and allele frequency was observed for eNOS G894T but not for T-786C and 4a/4b polymorphisms. At the multivariate analysis after adjustment for traditional vascular risk factors and other atherosclerotic localizations, the eNOS 894T variant was significantly associated with AAA, according to dominant and recessive models (dominant model odds ratio [OR]: 2.2, 95% confidence interval [CI]: 1.21-3.93, P = .007; recessive model OR: 2.7, 95% CI: 1.42-5.20, P = .002). When patients with other atherosclerotic localizations were excluded from the analysis, the 894T variant still remained associated with the predisposition to AAA, according to the models considered (dominant model OR: 2.1, 95%CI: 1.23-3.92, P = .007; recessive model OR: 2.8, 95%CI: 1.45-5.24, P = .002).


CONCLUSIONS
The present study showed that the eNOS G894T polymorphism is a mild modulator of the predisposition to AAA apart from traditional risk factors, suggesting a genetic influence on the molecular mechanisms responsible for this complex disease.
Fatini
Cinzia
C
Department of Medical and Surgical Critical Care, University of Florence, Thrombosis Centre, Italy.
Sofi
Francesco
F
Sticchi
Elena
E
Bolli
Paola
P
Sestini
Ilaria
I
Falciani
Michela
M
Azas
Leonidas
L
Pratesi
Giovanni
G
D000368:Aged; D000369:Aged, 80 and over; D017544:Aortic Aneurysm, Abdominal / Q000235:genetics*; D016009:Chi-Square Distribution; D005260:Female; 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; D012307:Risk Factors; D018709:Statistics, Nonparametric
D019001:Nitric Oxide Synthase