APOLIPOPROTEIN-B AND APOLIPOPROTEIN-E GENE POLYMORPHISMS AND ASSOCIATION WITH PLASMA-LIPIDS AND ATHEROSCLEROTIC-DISEASE IN FAMILIAL HYPERCHOLESTEROLEMIA

In 99 unrelated patients with heterozygous familial hypercholesterolem ia (FH), we studied the association between polymorphic variation in t he apolipoprotein B (ape B) (XbaI RFLP in exon 26 and Ins/Del 9-bp len gth polymorphism in exon 1) and apolipoprotein E (ape E) (epsilon(2), epsilon(3), epsilon(4)) genes and plasma lipoproteins. In contrast to a reference population of 464 Danish males, there was no association b etween polymorphic apo B and apo E gene variation and lipid variation in FH patients. Thus, minor gene effects on interindividual variation in lipid concentrations may be masked in the presence of a major gene defect of lipid metabolism such as FH. Although not associated with hi gher lipid concentrations, the epsilon(4) allele was more frequent in FH subjects with atherosclerotic disease than in the Danish reference population (P = 0.013). Also, FH subjects with atherosclerotic disease were older (53.2+/-10.9 years vs 45.8+/-14.4 years, P = 0.005), had h igher plasma cholesterol (11.0 +/- 2.0 mmol/l vs 10.3+/-1.9 mmol/l, P = 0.065), lower HDL cholesterol (1.21+/-0.36 mmol/l vs 1.35+/-0.34 mmo l/I, P = 0.062), and higher triglyceride concentrations (1.8 +/- 1.7 m mol/l vs 1.3+/-1.6 mmol/l; P = 0.004) than FH subjects without atheros clerotic disease.