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

Abstract

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.

• Authors: Raul D Santos, Ernst J Schaefer, Bela F Asztalos, Eliana Polisecki, Jian Wang, Robert A Hegele, Lilton R C Martinez, Marcio H Miname, Carlos E Rochitte, Protasio L Da Luz, Raul C Maranhão
• Journal: Journal of lipid research (J Lipid Res) Vol. 49 Issue 2 Pg. 349-57 (Feb 2008) ISSN: 0022-2275 [Print] United States
• PMID: 17991756 (Publication Type: Case Reports, Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.)

Chemical References

• Apolipoprotein A-I
• Cholesterol, HDL
• Lipoproteins, HDL

Topics

• Adult
• Aged
• Apolipoprotein A-I (blood, deficiency, genetics)
• Child
• Child, Preschool
• Cholesterol, HDL (blood)
• Female
• Humans
• Hypolipoproteinemias (blood, genetics, metabolism)
• Lipoproteins, HDL (blood, chemistry)
• Male
• Particle Size
• Pedigree
• Xanthomatosis (metabolism)