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1 CNR Institute of Clinical Physiology, G. Pasquinucci Hospital, Via Aurelia SUD-Montepepe, 54100 Massa, Italy
aAuthor for correspondence. Fax 39-585-493601; e-mail colombo{at}ifc.pi.cnr.it.
Background: Endothelial nitric oxide synthase (eNOS) could be a candidate gene for coronary artery disease (CAD). This study investigated the relationship of the eNOS Glu298
Asp and T786C polymorphisms with the presence and severity of CAD in the Italian population.
Methods: We enrolled 415 unrelated individuals who underwent coronary angiography. The severity of CAD was expressed by means of the Duke score. The eNOS Glu298Asp and T786C variants were analyzed by PCR.
Results: There was significant linkage disequilibrium between the two eNOS polymorphisms (P <0.0001). Both variants were significantly associated with the occurrence and severity of CAD (P = 0.01 and 0.004 for Glu298Asp and T786C, respectively). The risk of CAD was increased among individuals homozygous for the C allele of the T786C polymorphism compared with individuals homozygous for the T allele (odds ratio = 2.5; P <0.01) and was independent of the other common risk factors (P = 0.04). Moreover, individuals with both the Asp/Asp genotype of the Glu298Asp polymorphism and at least one C allele of the T786C variant in the promoter region of the eNOS gene had an increased risk of CAD (odds ratio = 4.0; P <0.001) and a significantly higher mean Duke score (26.2 ± 2.9 vs 45.2 ± 3.7; P = 0.002) compared with individuals with the TT genotype and the Glu allele.
Conclusions: The present study provides evidence that the Glu298Asp and T786C polymorphisms of the eNOS gene are associated with the presence and severity of angiographically defined CAD in the Italian population and that those individuals carrying both eNOS variants simultaneously might have a higher risk of developing CAD.
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