GENETIC EPIDEMIOLOGY OF LOW-DENSITY-LIPOPROTEIN SUBCLASS PHENOTYPES

Heterogeneity in LDL particles can be described by two distinct phenotypes in individual subjects, denoted A and B, based on gradient gel electrophoresis. Phenotype A is characterized by a predominance of large, buoyant LDL particles, while phenotype B is characterized by a predominance of small, dense LDL particles. Several studies have demonstrated that LDL subclass phenotype B is associated with both increased risk of coronary heart disease and an atherogenic lipoprotein profile. Complex segregation analyses in families, heritability analyses in twins, and recent linkage analyses, uniformly support the presence of genetic influences on LDL subclass phenotypes. However, environmental and behavioural influences on LDL subclasses have also been documented. Understanding the mechanisms underlying LDL subclass phenotypes may lead to targeted intervention to reduce coronary heart disease (CHD) risk in genetically susceptible individuals. Thus, LDL subclass phenotypes represent a common, genetically-influenced risk factor for coronary heart disease.