Prognostic Implications of Genetics in Cardiovascular Disease

Pieter   A.   Doevendans; Jasper   van der   Smagt; Peter      Loh; Nicolaas   de   Jonge; Daniel   J.   Touw

Abstract

The monogenetic cause of familial cardiovascular disease is being unraveled at a rapid pace. Gradually, the scope is moving from mono- to multigenetic analysis of diseases, like atherosclerosis and hypertension. The multigenic approach brings unexpected genes to the spotlight not only as relevant etiologic factors, but also as potential therapeutic targets. To understand the sensitivity of an individual for medical treatment, it is important to study gene expression in relation to treatment. The importance of this approach has been demonstrated for statin treatment as these compounds have beneficial effects on endothelial nitric oxide synthase transcription, in addition to lowering of cholesterol. However, the impact of the statin treatment can be modified by genetic variation in, for instance, the nitric oxide gene, and also in genes involved in cholesterol metabolism. These genes have a direct link to cardiovascular disease. Response to drugs however, is also dependent on general enzyme activity, which determines the rate of drug metabolism. Our knowledge on these subjects is very limited, but some of the more interesting observations are discussed here. Any review is incomplete without considering the relation between genetic variation and environment, or more specifically the cardiovascular risk factors. These topics are briefly addressed for the different cardiovascular entities including; atherosclerosis, hypertension, cardiac failure and arrhythmias.

Keywords: polymorphisms, genetics, metabolism, prognosis