title: Apolipoprotein A-I deficiency. Biochemical and metabolic characteristics.
abstract: Familial HDL deficiencies are associated with variable susceptibility to premature coronary heart disease, but the mechanism underlying this association remains poorly understood. Three homozygotes with isolated complete apo A-I deficiency caused by an autosomal codominant apo A-I Q[-2]X mutation and one heterozygote developed coronary heart disease before age 40 years. We characterized the effects of this mutation on lipoprotein metabolism. LDL FC, phospholipid, and apo B were all significantly higher in homozygotes than in heterozygotes. The HDLs of the heterozygotes were apo A-I poor relative to apo A-II. Lecithin-cholesterol acyltransferase activity was 59% lower in homozygotes than in normal subjects or heterozygotes. Cholesteryl ester transfer activity was increased in a homozygote compared with a normolipidemic control subject. Postprandial lipid metabolism was studied in one homozygote and one heterozygote. Post-prandial TG response in the homozygote was significantly exaggerated, while residual plasma HDL level remained unaffected. The homozygote also had delayed clearance of retinyl ester, a marker of chylomicron remnant metabolism. Thus, homozygosity and heterozygosity for apo A-I Q[-2]X are associated with qualitative, as well as quantitative, disturbances in plasma HDLs, LDLs, lipid-modifying enzyme activities, and postprandial retinyl ester metabolism. The observed elevation of atherogenic lipoproteins and reduction in antiatherogenic lipoproteins in the affected members of the apo A-I Q[-2]X kindred are consistent with the primary deficiency in apo A-I having pleiotropic effects that markedly enhance susceptibility for coronary heart disease.
mesh_terms: D016632:Apolipoprotein A-I / Q000097:blood / Q000172:deficiency*; D016633:Apolipoprotein A-II / Q000097:blood; D001055:Apolipoproteins B / Q000097:blood; D002784:Cholesterol / Q000097:blood; D004224:Diterpenes; D005260:Female; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D008074:Lipoproteins / Q000378:metabolism*; D008075:Lipoproteins, HDL / Q000097:blood; D008077:Lipoproteins, LDL / Q000097:blood; D008297:Male; D009154:Mutation; D007862:Phosphatidylcholine-Sterol O-Acyltransferase / Q000097:blood; D010743:Phospholipids / Q000097:blood; D000084562:Retinyl Esters; D014280:Triglycerides / Q000097:blood; D014801:Vitamin A / Q000031:analogs & derivatives / Q000097:blood
chemical_list: D016632:Apolipoprotein A-I; D016633:Apolipoprotein A-II; D001055:Apolipoproteins B; D004224:Diterpenes; D008074:Lipoproteins; D008075:Lipoproteins, HDL; D008077:Lipoproteins, LDL; D010743:Phospholipids; D000084562:Retinyl Esters; D014280:Triglycerides; D014801:Vitamin A; C014794:retinol palmitate; D002784:Cholesterol; D007862:Phosphatidylcholine-Sterol O-Acyltransferase