Genetic aspects of arteriosclerosis.

Abstract

This review discusses the genetic factors in the development of arteriosclerosis and coronary heart disease (CHD). In several studies, multivariate analysis of prospective mortality/morbidity data and angiographic findings have indicated that a family history of CHD contributed to CHD risk independently of the established risk factors. In addition, ethnic groups that differ in the prevalence and incidence of CHD also markedly differ in blood groups and protein-enzymatic markers. These or other genetic differences may affect CHD rates. Data from fraternal and identical twins, the source of some early genetic CHD findings, are reviewed. Genetic disorders of lipoprotein metabolism and transport, such as familial hypercholesterolemia, as well as other monogenic disorders are discussed. The role of apoprotein E polymorphism i other monogenic disorders are discussed. The role of apoprotein E polymorphism in determining plasma LDL variability among individuals is considered. Recombinant DNA technology, molecular cloning, and the identification of restriction fragment length polymorphisms are new tools for investigators who assess DNA polymorphism. Recent advances in that domain include: DNA polymorphisms affecting blood levels of apo A-I and A-II, association of a DNA insertion on chromosome 19 with severe premature atherosclerosis, and information concerning linkage of the genes for various apolipoproteins. In addition, the evidence for a major genetic component in diabetes mellitus and research into the genetic aspects of hypertension are reviewed. The male/female ratio in pathologically and epidemiologically assessed atherosclerosis may provide clues to the role of genetics. Early structural changes in the coronary artery intima are compatible with the ethnic and gender predilection. A key question in understanding underlying mechanisms in atherosclerosis is why coronary arteries are occluded in individuals whose other arterial systems are largely unaffected. The review concludes with a discussion of the directions and implications of future genetic research in arteriosclerosis with an emphasis on uncovering genetically determined differences in arterial wall response to blood flow. Subpopulations with different genetic risks may be identified, in which case universal preventive strategies might be replaced with specific ones.