Genetic and environmental influences on LDL subclass phenotypes.

There is accumulating evidence that subclasses of low-density lipoproteins (LDL) are important in atherosclerosis. Several case-control studies have demonstrated that a predominance of small, dense LDL (LDL subclass phenotype B) is associated with increased risk of coronary heart disease (CHD). Phenotype B is also consistently characterized by an atherogenic lipoprotein phenotype, including increased levels of plasma triglyceride and decreased high-density lipoprotein cholesterol. Family studies and genetic linkage studies demonstrate that LDL subclasses are influenced by a single major gene effect, although this locus (or loci) remain to be definitively mapped. Twin studies confirm the presence of genetic effects, but also show that non-genetic influences are important. Hypolipidemic drugs, beta-blockers, diet and exercise, in particular, appear to influence the expression of LDL subclass phenotypes. This combination of genetic and environmental influences may provide opportunities to develop targeted intervention strategies to reduce CHD risk among genetically susceptible individuals.