High density lipoprotein in familial apoprotein aI deficiency

Abstract EN

Our aim was to characterize HDL in a kindred with familial apolipoprotein AI (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 -3 migrating apoA-II particles, and only modestly decreased normal amounts of slow migrating apoA-IV- and apoE-containing HDL, while in the eight heterozygotes, there was loss of large -1 HDL particles.

Our data indicate that isolated apoA-I deficiency results in marked HDL deficiency with very low apoA-II -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.