Influence of endothelial nitric oxide synthase gene polymorphisms (G894T, 4a4b, T-786C) and hyperhomocysteinemia on the predisposition to acute coronary syndromes.
BACKGROUND
Nitric oxide is an endothelium-derived relaxing factor that contributes significantly to vascular tone regulation. In this study we investigated the role of endothelial nitric oxide synthase (eNOS) polymorphisms as predisposing factors to acute coronary syndromes (ACS).


METHODS
In 477 consecutive patients admitted to the coronary intensive therapy unit of the University of Florence and in 537 unrelated controls, genotypes of eNOS G894T and T-786C polymorphisms were determined by polymerase chain reaction-restriction fragment length polymorphism analysis and the repeat polymorphism 4a/4b was analyzed by polymerase chain reaction. The genotype distribution was in Hardy-Weinberg equilibrium for all variants.


RESULTS
The multivariate analysis showed that the homozygosity for the eNOS 4a rare variant represented an independent predisposition factor to ACS (odds ratio [OR] 2.5, 95% CI 1.1-5.4, P =.02) and in particular influenced the risk of acute myocardial infarction (OR 3.6, 95% CI 1.2-11.5, P =.03). Subjects carrying the 4a4a/-786CC haplotype showed a higher predisposition to the disease (OR 6.1, 95% CI 1.3-29.6, P =.02). The contemporary presence of hyperhomocysteinemia and homozygosity for the -786C variant influenced the predisposition to ACS (OR 9.1, 95% CI 1.7-46.7, P =.008).


CONCLUSIONS
The presence of the eNOS 4a4a genotype represents a predisposing condition to ACS and in particular to acute myocardial infarction. Moreover, our data provide the evidence that the -786CC pattern modulates the susceptibility to ACS in 4a4a homozygotes and in hyperhomocysteinemic patients.
Department of Medical and Surgical Critical Care, Section of Clinical Medicine and Cardiology, Thrombosis Centre, Azienda Ospedaliera Careggi, Florence, Italy. cinziafatini@hotmail.com
Cinzia
C
Fatini
Francesco
F
Sofi
Elena
E
Sticchi
Francesca
F
Gensini
Anna Maria
AM
Gori
Sandra
S
Fedi
Ilaria
I
Lapini
Carlo
C
Rostagno
Marco
M
Comeglio
Daria
D
Brogi
Gianfranco
G
Gensini
Rosanna
R
Abbate
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000789:Angina, Unstable / Q000209:etiology / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D006720:Homozygote; D006801:Humans; D020138:Hyperhomocysteinemia / Q000150:complications*; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009154:Mutation; D009203:Myocardial Infarction / Q000209:etiology / Q000235:genetics*; D019001:Nitric Oxide Synthase / Q000235:genetics*; D016017:Odds Ratio; D011110:Polymorphism, Genetic; D012307:Risk Factors
D019001:Nitric Oxide Synthase