Associations with the Glu298Asp polymorphism and cardiovascular disease have been reported in many studies (95,96), The Asp298 polymorphism has been shown to have significantly higher (P = 0.001) median plasma NOx than those without this mutation (97). How this reflects NO levels in the vasculature is unclear.
Leeson et al. (98) studying vascular function by endothelium-dependent, flow-mediated brachial artery dilatation (FMD) and endothelium-independent dilatation response to glyceryl trinitrate observed that vascular function was lower in Asp298 carriers, particularly in smokers and that n-3 fatty acids had a positive effect in this group, but not in Glu298 homozygotes.
Not all studies have shown positive associations: Nassar et al. (99) examined the prevalence of this polymorphism in patients with early-onset coronary artery disease (CAD) compared with those manifesting CAD later in life and found no association of the eNOS Asp298 allele with premature CAD, no association was found in a Taiwanese population (100), or a Finnish population (101).
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