Serum low density lipoprotein cholesterol level and cholesterol absorption efficiency are influenced by apolipoprotein B and E polymorphism and by the FH-Helsinki mutation of the low density lipoprotein receptor gene in familial hypercholesterolemia.

The aim of the present study was to evaluate the effect of variation of different gene loci separately and in concert on lipid metabolism in heterozygous familial hypercholesterolemia (FH). We assayed a unique low density lipoprotein (LDL) receptor gene defect (designated as FH-Helsinki), the XbaI polymorphism of the apolipoprotein (apo) B, phenotypes of the apo E, and determined the levels of serum lipoproteins, the efficiency of cholesterol absorption, and the values for several parameters of cholesterol metabolism in 51 unrelated patients with heterozygous FH. The genetic parameters were distributed independently of each other. Gender distribution and the prevalence of coronary artery disease were similar in the different apo E phenotypes, in the apo B genotypes, and in patients with and without the FH-Helsinki mutation. However, the FH-Helsinki mutation was associated with an increased body mass index. Serum LDL cholesterol was significantly elevated in patients with the FH-Helsinki mutation and the apo B X2 allele. Apo E phenotypes were not related to serum lipids per se, but the highest serum LDL cholesterol levels were measured in patients with the FH-Helsinki gene, apo E4 phenotype, and at least one X2 allele. Patients with the FH-Helsinki mutation and apo E4 phenotype had the highest cholesterol absorption efficiency. Cholesterol absorption was not related to serum lipids or lipoproteins, but LDL cholesterol was most elevated in patients with the most efficient cholesterol absorption. We conclude that in FH, diverse genetic factors exert individual and additive influences on serum LDL cholesterol levels.