Genetic regulation of endothelial function

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Abstract
Children with certain single gene disorders such as homocystinuria and familial hypercholesterolaemia, at risk of premature atherosclerosis, also exhibit early endothelial dysfunction.5, 6 Although the more common forms of atherosclerosis manifest later in life, twin and adoption studies indicate that this more common form is also partly heritable,7 though inheritance is complex, arising as a result of common environmental exposures (risk factors) and many common gene variants (polymorphisms) with small to moderate effect. In common with other complex disorders, the causative genes have been difficult to identify. There have been few studies evaluating the heritability of endothelial function. However, vessels in the offspring or relatives of patients with premature cardiovascular disease show structural and functional changes more commonly, even before clinically manifest disease.8, 9 Therefore, individual differences in endothelial function, and hence susceptibility to later atherosclerosis, might relate not only to different levels of exposure to risk factors but also to inter-individual differences in the carriage of risk alleles of genes expressed in the vascular endothelium. The atheroprotective actions of endothelial mediators such as NO suggest that genes that regulate synthesis and inactivation of these mediators might be important. Thus far, studies to address this have been small, and the findings are inconsistent probably because the genetic effect sizes in question are probably smaller then previously appreciated. There is now an increasing realisation that genetic studies, whether of intermediate phenotypes or of clinical outcomes, need to be much larger to provide reliable assessment of small but potentially important genetic effects.10 This article provides a brief overview of the most studied genes.

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