Characterization of high density lipoprotein particles in familial apolipoprotein A-I deficiency

• Published in: Journal of lipid research Vol. 49; no. 2; pp. 349 - 357
• Main Authors: Santos, Raul D, Schaefer, Ernst J, Asztalos, Bela F, Polisecki, Eliana, Wang, Jian, Hegele, Robert A, Martinez, Lilton R C, Miname, Marcio H, Rochitte, Carlos E, Da Luz, Protasio L, Maranhão, Raul C
• Format: Journal Article
• Language: English
• Published: United States 01.02.2008
• Subjects: Adult; Aged; Apolipoprotein A-I - blood; Apolipoprotein A-I - deficiency; Apolipoprotein A-I - genetics; Child; Child, Preschool; Cholesterol, HDL - blood; Female; Humans; Hypolipoproteinemias - blood; Hypolipoproteinemias - genetics; Hypolipoproteinemias - metabolism; Lipoproteins, HDL - blood; Lipoproteins, HDL - chemistry; Male; Particle Size; Pedigree; Xanthomatosis - metabolism
• ISSN: 0022-2275
• DOI: 10.1194/jlr.M700362-JLR200

Our aim was to characterize HDL subspecies and fat-soluble vitamin levels in a kindred with familial apolipoprotein A-I (apoA-I) deficiency. Sequencing of the APOA1 gene revealed a nonsense mutation at codon -2, Q[-2]X, with two documented homozygotes, eight heterozygotes, and two normal subjects in the kindred. Homozygotes presented markedly decreased HDL cholesterol levels, undetectable plasma apoA-1, tuboeruptive and planar xanthomas, mild corneal arcus and opacification, and severe premature coronary artery disease. In both homozygotes, analysis of HDL particles by two-dimensional gel electrophoresis revealed undetectable apoA-I, decreased amounts of small alpha-3 migrating apoA-II particles, and only modestly decreased normal amounts of slow alpha migrating apoA-IV- and apoE-containing HDL, while in the eight heterozygotes, there was loss of large alpha-1 HDL particles. There were no significant decreases in plasma fat-soluble vitamin levels noted in either homozygotes or heterozygotes compared with normal control subjects. Our data indicate that isolated apoA-I deficiency results in marked HDL deficiency with very low apoA-II alpha-3 HDL particles, modest reductions in the separate and distinct plasma apoA-IV and apoE HDL particles, tuboeruptive xanthomas, premature coronary atherosclerosis, and no evidence of fat malabsorption.