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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)
 
 
 

The T-786C endothelial nitric oxide synthase genotype is a novel risk factor for coronary artery disease in Caucasian patients of the GENICA study.

OBJECTIVES: 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.[1]

References

  1. The T-786C endothelial nitric oxide synthase genotype is a novel risk factor for coronary artery disease in Caucasian patients of the GENICA study. Rossi, G.P., Cesari, M., Zanchetta, M., Colonna, S., Maiolino, G., Pedon, L., Cavallin, M., Maiolino, P., Pessina, A.C. J. Am. Coll. Cardiol. (2003) [Pubmed]
 
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