Genetic determinants of atherosclerosis-related dyslipidemias and their clinical implications

New approaches to the study of the genetics of premature coronary heart disease (CHD) have been made possible by the introduction of DNA probes for the apolipoproteins, the receptors and enzymes involved in lipid transport. Initially these were used to identify restriction fragment length polymorphisms for use as genetic markers to locate genes involved in the pathogenesis of atherosclerosis. More recent developments have allowed direct analysis of etiological mutations by such methods as single stranded conformational polymorphism (SSCP) analysis and denaturing gradient gel electrophoresis (DGGE). Loci that have been incriminated by such techniques include the apolipoprotein A-I--C-III--A-IV gene cluster, the apo B gene and the lipoprotein lipase locus. It is to be anticipated that these and other techniques will eventually identify all the major determinants involved in disorders of lipid transport and the development of premature atherosclerosis.