Variation of apolipoprotein B as a possible cause of decreased low densitylipoprotein clearance and hypercholesterolemia

The fractional catabolic rate (FCR) for low density lipoprotein (LDL) apoli poprotein B (apo B) was studied to explore the variations in apo B as a pos sible cause of hypercholesterolemia. The FCR of radioiodine labelled autolo gous LDL and homologous LDL isolated from a normocholesterolemic subject we re compared in forty-nine type II hypercholesterolemic males and females wi th the mean plasma concentration of total cholesterol of 7.78 mmol/l, LDL-c holesterol 5.41 mmol/l and triglycerides 2.09 mmol/l. In most patients the autologous LDL was catabolized at an equal rate and sometimes even faster t han the homologous LDL. However, twelve out of forty-nine patients cataboli zed homologous LDL 0.8-19.3% faster than autologous LDL and several apo B p olymorphisms were determined. No apo B-3500 or apo B-3531 mutations were de tected. Patients with XbaI -/- (absence of cutting site) had lower total, I DL and LDL cholesterol and LDL apoB than the other genotypes. Patients with EcoRI +/+ (presence of cutting site) had higher total, VLDL and LDL choles terol and slower FCR for autologous LDL, and their VLDL was richer in chole sterol than that of patients with the EcoRI +/-. The MspI and ins/del polym orphisms were nor associated with variations in the measured parameters. Th e apo E 4 was associated with higher VLDL and IDL cholesterol, higher trigl ycerides and LDL apo B than E 3/3. Overall, the determined apo B polymorphi sms were not related to the slow clearance of autologous LDL among the 12 p atients, in whom autologous LDL was cleared at a slower rate than homologou s LDL. In conclusion, hypercholesterolemia can be due to particle-related s low clearance of LDL in some patients. However, this is not a common cause of hypercholesterolemia. (C) 1999 Elsevier Science Ireland Ltd. All rights reserved.