Genes and the vascular endothelium

Genetic variation within the population determines endothelial responses and therefore has the potential to modify both atherogenesis as well ashow an individual responds to risk factors. It is estimated that around 10-20% of the variation in endothelial function may be accounted for by genetic variation. The impact of genetic variation on a range of endothelial intermediate phenotypes has been studied and the main genes of interest have been: the NOS3 gene that encodes eNOS; DDAH1 and 2 that encode dimethylarginine dimethylaminohydrolases (DDAH); CYBA gene that encodes NADPH oxidase and especially its p22phox subunit polymorphisms; SOD3 that encodes extracellular superoxide dismutase (ecSOD); genetic changes in GTP cyclohydrolase-1 (GCH-1) that plays a key role in the biosynthesis of tetrahydrobiopterin (BH4); genetic changes in methylenetetrahydrofolate reductase (MTHFR) that regulates circulating homocysteine levels; endothelin-1 gene (EDN) and the receptors genes for endothelin EDRNA and B that control endothelin and its function. Genetic variation relevant to the endothelium has not proved to be an effective predictor of risk. Recent genome wide association studies have identified a range of novel loci relevant to cardiovascular disease and, in the future, investigations of these loci may identify novel pathways that exert an influence on disease progression through endothelial responses. ©2011 Nova Science Publishers, Inc. All rights reserved