出版社：American Society for Biochemistry and Molecular Biology
摘要：Apolipoprotein (apo)A-I is the major protein component of HDL and the cofactor for LCAT. We describe a large Spanish kindred, living in the Mediterranean Island of Mallorca, that presents a dominant form of hypoalphalipoproteinemia. The lipid profile of this family was studied because the proband, a 40-year-old male presenting signs of coronary atherosclerosis, showed severe HDL deficiency. However, none of the other family members had a known history of cardiovascular disease. Sequence analysis of the apoA-I gene in affected members identified a 33-base pair deletion, corresponding to residues 165–175 of the mature protein, eliminating the first 11 amino acids of the internal repeat 7. ApoA-IMALLORCA is associated with HDL-cholesterol deficiency (concentration ranging from 8–48% of the value in non-carriers), and a 2- to 3-fold decrease in plasma concentrations of apoA-I and apoA-II and endogenous LCAT activity, concomitant with a slight decrease in serum cholesterol efflux capability. Impairment of LCAT activity in HDL particles containing only mutated forms of apoA-I would not explain a pattern of dominant inheritance. HDL particles containing wild type apoA-I and at least one mutant apoA-I may also present impaired LCAT activity and/or other alterations leading to defective HDL maturation, a situation that would increase HDL lipid catabolism. We conclude that amino acids 165–175 of apoA-I are critical for normal HDL metabolism, at least in part because of their role in LCAT activation. However, apoA-IMALLORCA is not necessarily associated with clinical signs of atherosclerosis. —Martín-Campos, J. M., J. Julve, J. C. Escolà, J.Ordóñez-Llanos, J. Gómez, J. Binimelis, F. González-Sastre, and F. Blanco-Vaca. ApoA-IMALLORCA impairs LCAT activation and induces dominant familial hypoalphalipoproteinemia. J. Lipid Res. 2002. 43: 115–123.
关键词：apolipoprotein ; atherosclerosis ; coronary heart disease ; high density lipoprotein ; molecular diagnosis
