Genotypic and phenotypic variation in familial hypercholesterolemia.

Familial hypercholesterolemia is characterized by an increase in low density lipoprotein (LDL) cholesterol, tendon xanthomata, and premature atherosclerosis. In homozygotes, phenotypic expression of the disorder is dominated by genotypic variation at the LDL-receptor gene locus, with other influences, like gender, exerting relatively little effect. In contrast, phenotypic variation in heterozygotes is influenced not only by the nature of the underlying gene mutation but also by gender, diet, and other forms of genetic polymorphism, including the apolipoprotein E genotype.