DOES THE PRESENCE OF THE 3500 MUTANT APOLIPOPROTEIN B-100 IN LOW-DENSITY-LIPOPROTEIN PARTICLES AFFECT THEIR ATHEROGENICITY

Apolipoprotein B-100 (ape B-100) is the protein component of low densi ty Lipoprotein (LDL) responsible for its binding and clearance by LDL receptors (LDL-R). In familial defective apo B-100 (FDB), a mutation i n apo B-100 at residue 3500 markedly reduces its affinity for LDL-R, o ften causing accumulation of defective LDL particles, and an increased proneness to coronary artery disease (CAD). In FDB heterozygotes, abo ut 70% of the LDL particles are mutant, which may alter their atheroge nicity relative to LDL containing normal apo B. Therefore, we compared CAD in heterozygous FDB with CAD in heterozygous familial hypercholes terolemia (FH), since raised LDL is usually present from birth in both conditions, and in FH the LDL particles that accumulate have normal a po B, as the inherited defect involves the LDL-R. The clinical present ation of coronary atherosclerosis and its angiographic appearance were examined in FDB and FH patients matched for conventional cardiac risk factors (hypertension, smoking, sex) and serum lipid levels. There wa s no significant difference between the FDB and FH patients (n = 11 pa irs) in the type of cardiac symptoms or their ages of onset (50 +/- 9 vs. 45 +/- 11 years). Coronary angiographic appearance was also simila r in both groups (n = 9 pairs). These observations suggest that LDL pa rticles with the 3500 mutation in apo B have the same atherogenicity a s LDL particles with normal apo B.