Endothelial nitric oxide synthase gene Glu298Asp polymorphism in patients with coronary artery disease.
OBJECTIVE
Endo-derived nitric oxide (NO) is synthesized from L-arginine by endothelial nitric oxide synthase (NOS3). Since reduced NO synthesis in endothelial cells has been implicated in the development of coronary atherosclerosis, we investigated the association of NOS3 gene polymorphisms and coronary artery disease (CAD) in an Iranian population.


METHODS
We studied the NOS3 gene Glu298Asp polymorphism in 241 CAD patients with positive coronary angiograms (i.e.,> 50% stenosis affecting at least one coronary vessel) in Shahid Rajaee Heart Hospital and 261 control subjects without a history of symptomatic CAD. The NOS3 gene polymorphism was analyzed by polymerase chain reaction and restriction fragment length polymorphism. Lipid profile and other risk factors were also determined.


RESULTS
The genotype frequencies of Glu298Asp polymorphism for Glu/Glu, Glu/Asp, and Asp/Asp were 61.3%, 32.2%, and 6.5%, respectively, in control subjects, and 46.5%, 42.7%, and 10.8% in CAD patients, respectively. The genotype frequencies differed significantly between the two groups (P=.003). The frequencies of the Asp alleles were 32.2% and 22.6% for CAD patients and control subjects, respectively; the difference between the two groups was statistically significant (P=.001; odds ratio=1.6). Plasma lipids, except HDL-C, were also significantly increased in the CAD groups.


CONCLUSIONS
These results suggest that CAD is associated with Glu298Asp polymorphism of the NOS3 gene in our population and that this polymorphism is an independent risk factor for CAD.
Salimi
Saeedeh
S
Cellular and Molecular Research Center, Department of Biochemistry, School of Medicine, Zahedan University of Medical Sciences, Zahedan, Iran. sasalimi@yahoo.com
Firoozrai
Mohsen
M
Zand
Hamid
H
Nakhaee
Alireza
A
Shafiee
Sayed M
SM
Tavilani
Heidar
H
Mohebbi
Ahmad
A
D000704:Analysis of Variance; D001120:Arginine / Q000378:metabolism; D016022:Case-Control Studies; D016001:Confidence Intervals; D003324:Coronary Artery Disease / Q000201:enzymology / Q000453:epidemiology / Q000235:genetics*; D004730:Endothelium, Vascular / Q000201:enzymology* / Q000378:metabolism; D005260:Female; D006801:Humans; D007492:Iran / Q000453:epidemiology; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D052250:Nitric Oxide Synthase Type III / Q000235:genetics* / Q000378:metabolism; D016017:Odds Ratio; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D012150:Polymorphism, Restriction Fragment Length; D012307:Risk Factors
D001120:Arginine; D052250:Nitric Oxide Synthase Type III