Familial defective apolipoprotein B-100 (R3500Q) in Northern Ireland

Familial defective apolipoprotein B-100 (FDB) R3500 is an autosomal co-domi nant disorder caused by the substitution of glutamine for arginine at amino acid residue 3500 of the apolipoprotein B-100 gene. It is associated with hypercholesterolaemia of varying severity, and with coronary artery disease . Hypercholesterolaemic patients (n = 158) from Northern Ireland were scree ned for the defect by polymerase chain reaction-mediated, site-directed mut agenesis. Clinical presentation ranged from moderate hypercholesterolaemia with a family history of hypercholesterolaemia or heart disease (n = 104) t o those classified as definitely having familial hypercholesterolaemia (FH) (n = 54). Eight (5.1%) unrelated individuals were found to be heterozygous for the FDB R3500Q mutation, including two (3.7%) of those 54 classified c linically as having FI-I. Treatment with HMG-CoA-reductase-inhibiting drugs (statins) decreased total cholesterol by 22-44% and low-density lipoprotei n cholesterol by 34-46% in all but one FDB heterozygote.