Major apolipoprotein B-100 mutations in lipoprotein metabolism and atherosclerosis.
Familial defective apolipoprotein B-100 (FDB) is an autosomal dominant disorder associated with hypercholesterolaemia in which an aminoacid substitution in apoprotein B-100 leads to low-density lipoprotein (LDL) particles which have defective binding to the LDL receptor. All known patients are heterozygous, and their plasma contains normal and poorly binding LDL particles. 12 hypercholesterolaemic patients from 10 unrelated families with FDB were treated with lovastatin. In 6 patients treated with 20 mg lovastatin daily, LDL cholesterol decreased by 21.5% from 6.23 to 4.89 mmol/l (95% confidence interval 0.74, 1.96 mmol/l), whereas it fell by 32.1%, from 6.99 to 4.81 mmol/l (95% CI 1.55, 2.70 mmol/l), in 9 patients who received 40 mg daily. These results indicate that the hypercholesterolaemia of FDB may respond to treatment with statins.