Genetic determinants of arterial properties and of heart disease

It has been known for a long time that arterial properties are strongly genetically determined: total heritability of arterial stiffening, independently of other factors, is estimated to be 30e40%. It is also interesting that telomeric length, a heritable indicator of biological ageing, has been found to correlate with increased arterial stiffening. Large amount of data on genetics of arterial stiffness has been published and various genetic methods were used including genome-wide association studies; despite these modern genetic technologies, the candidate gene approach gives us up to now the most relevant information. The list of genes potentially involved is long. From pathophysiological point of view, arterial stiffening is the consequence of altered structure and function of extracellular matrix, cellular growth and their interaction in the vascular wall. Therefore, a large group of genes potentially involved are the genes coding for extracellular matrix components. This group includes genes coding for elastin and fibrillin-1, type 1 collagen, and matrixmetalloproteinase 3 and 9. A number of systems regulating the circulation globally influence vascular wall properties, and therefore, a group of nonmatrix genes play a role as well. Among them, the genes coding for components of renineangiotensinealdosterone system (RAAS) seems to be of primary importance. There are also data on genes coding for sympathetic nervous system (beta 1, 2 and 3 adrenergic receptors), nitric oxide synthase, endothelin and its receptors, guanine nucleotide regulatory proteins (G-proteins), estrogen receptors alpha, adhesion molecules (ICAM1 and VCAM1) and several others. This article cannot give exhaustive information on this very large field. It deals with several genes with common