The T-786C endothelial nitric oxide synthase genotype is a novel risk factor for coronary artery disease in Caucasian patients of the GENICA study.
OBJECTIVE
We investigated the association of polymorphisms in the promoter region and exon 7 endothelial nitric oxide synthase (eNOS) gene with coronary artery disease (CAD).


BACKGROUND
Endothelial dysfunction foretells cardiovascular events and can be genetically determined.


METHODS
We genotyped for the promoter (T(-786)C) and exon 7 (Glu298Asp, G(894)T) polymorphisms in 1,225 subjects; 1,106 were consecutive patients undergoing coronary angiography and 119 control subjects without any cardiovascular risk factors. Genotyping was performed with melting curve analysis of polymerase chain reaction products from allele-specific acceptor and donor probes that were 5'- and 3'-end labeled with LCRed640 and fluorescein, respectively; CAD was assessed by quantitative coronary angiography. We performed multiple logistic regression analysis for the effect of the T(-786)C, the missense Glu298Asp variant, and other coronary risk factors on two- and three-vessel CAD.


RESULTS
The overall genotype distribution of T(-786)C (CC = 17.7%, CT = 40.4%, and TT = 41.9%) and Glu298Asp (GG = 43.3%, GT = 37.0%, and TT = 19.7%) was consistent with the Hardy-Weinberg equilibrium. The regression analysis showed that the T(-786)C, but not the missense Glu298Asp variant, significantly predicted CAD, independent of other risk factors. Compared with TT homozygous, subjects carrying the C allele had a significant (p = 0.002) increase in the odds ratio of harboring two- or three-vessel CAD of 1.672 (95% confidence interval, 1.062 to 2.527). A subgroup analysis confirmed this effect of the T(-786)C polymorphism in men (p = 0.007), cigarette smokers (p = 0.001), subjects older than 60 years of age (p = 0.007), with hypercholesterolemia (p = 0.011), low high-density lipoprotein cholesterol (p = 0.006), and overweight or with obesity (p = 0.041).


CONCLUSIONS
The C allele at the T(-786)C endothelial nitric oxide synthase polymorphism is associated with a higher risk of multivessel CAD in Caucasians.
Rossi
Gian Paolo
GP
Department of Clinical and Experimental Medicine, Clinica Medica 4 University Hospital, University of Padua, via Giustiniani 2, 35126 Padua, Italy. gianpaolo.rossi@unipd.it
Cesari
Maurizio
M
Zanchetta
Mario
M
Colonna
Stefania
S
Maiolino
Giuseppe
G
Pedon
Luigi
L
Cavallin
Martina
M
Maiolino
Pietro
P
Pessina
Achille C
AC
D000328:Adult; D000368:Aged; D017023:Coronary Angiography; D003324:Coronary Artery Disease / Q000000981:diagnostic imaging / Q000209:etiology / Q000235:genetics*; D005091:Exons / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D009569:Nitric Oxide / Q000235:genetics*; D019001:Nitric Oxide Synthase / Q000235:genetics*; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic / Q000235:genetics*; D011237:Predictive Value of Tests; D011401:Promoter Regions, Genetic / Q000235:genetics*; D011446:Prospective Studies; D012307:Risk Factors; D012720:Severity of Illness Index; D044465:White People / Q000235:genetics*
D009569:Nitric Oxide; D019001:Nitric Oxide Synthase