Genetics in childhood atherosclerosis

It is generally accepted that atherosclerosis is the extreme manifestation of what begins as a protective, fibroproliferative response to injury. Athe rosclerosis can become pathological as a result of chronic, excessive expos ure to particular causative agents. Several pathophysiological systems, inc luding the inflammatory response, the immune response, cellular growth and proliferation, lipoprotein metabolism and coagulation, each of which operat es as the result of the contributions of numerous gene products, can contri bute to atherosclerosis either individually or in concert. In theory, ident ifying the genetic component(s) of atherosclerosis has become possible with molecular technologies and analytical methods. Reductionist experimental m odels have produced a list of several hundred candidate genes for the study of the genetic component of atherosclerosis. Within some families and isol ated communities, the effect of a single gene upon atherosclerosis suscepti bility may be profound, such as in the case of mutations within the gene en coding the low density lipoprotein receptor. However, at the level of the g eneral population, particular candidate genes have small effects on atheros clerosis, or on one of its intermediate phenotypes. Furthermore, there are other factors, such as pleiotropy, epistasis, variations in genetic backgro und, differences in individual environmental landscape, non-linear interact ions among gene products and interactions between genes and the environment , which can confound the study of the genetic component of atherosclerosis. (C) 1999 Elsevier Science Ireland Ltd. All rights reserved.