Skip to main content
ARS Home » Northeast Area » Boston, Massachusetts » Jean Mayer Human Nutrition Research Center On Aging » Research » Publications at this Location » Publication #215330
Title: Characterization of High Density Lipoprotein Particles in Familial Apolipoprotein A-I Deficiency With Premature Coronary Atherosclerosis, Corneal Arcus and Opacification, and Tubo-Eruptive and Planar Xanthomas

Author
item SANTOS, RAUL - UNIVERSITY OF SAO PAULO
item Schaefer, Ernst
item Asztalos, Bela
item POLISECKI, ELIANA - TUFTS UNIVERSITY
item HEGELE, ROBERT - ROBARTS RESEARCH INST
item MARTINEZ, LILTON - UNIVERSITY OF SAO PAULO
item MINAME, MARCIO - UNIVERSITY OF SAO PAULO
item COIMBRA, SILMARA - UNIVERSITY OF SAO PAULO
item DA LUZ, PROTASIO - UNIVERSITY OF SAO PAULO
item MARANHAO, RAUL - UNIVERSITY OF SAO PAULO

Submitted to: Journal of Lipid Research
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 11/8/2007
Publication Date: 2/1/2008
Citation: Santos, R.D., Schaefer, E., Asztalos, B., Polisecki, E., Hegele, R.A., Martinez, L., Miname, M., Coimbra, S.R., Da Luz, P., Maranhao, R. 2008. Characterization of High Density Lipoprotein Particles in Familial Apolipoprotein A-I Deficiency With Premature Coronary Atherosclerosis, Corneal Arcus and Opacification, and Tubo-Eruptive and Planar Xanthomas. Journal of Lipid Research. 49(2):349-357.

Interpretive Summary: A low level of the good cholesterol particle or high density lipoprotein (HDL) cholesterol is an important heart disease risk factor. Here we study the amount of heart disease and the HDL particles in a family with very marked HDL deficiency, and loss of the abilty to make the major protein of HDL known A-I. We also define the gene defect, and document that there a three different kinds of HDL particles in the bloodstream- those containing A-I, those contain the E protein, and those contain the A-IV protein. It is know that HDL E is iumportant for the brain, while HDL A-I is important for the heart and arteries.

Technical Abstract: We describe two male siblings with homozygous familial apolipoprotein (apo) A-I deficiency, markedly decreased high density lipoprotein (HDL) cholesterol levels, undetectable plasma apoA-1, tubo-eruptive and planar xanthomas, and mild corneal arcus and opacification. Sequencing of the apoA-I gene revealed a nonsense mutation at codon -2, Q[-2]X, with two documented homozygotes, eight heterozygotes, and two normal subjects in the kindred. In 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 relatively normal amounts of slow alpha migrating apoA-IV and apoE containing HDL, while in the 8 heterozygotes there was loss of large alpha-1 HDL particles. The homozygous index case at age 39 years had a complete obstruction of his right coronary artery, high grade narrowing of his left anterior descending coronary artery, and had successful revascularization surgery. His homozygous brother had sustained a myocardial infarction, and undergone bypass surgery at age 38 years. In conclusion: 1) isolated apoA-I deficiency results in marked HDL deficiency with very low apoA-II alpha-3 HDL particles, and relatively normal apoA-IV and apoE HDL particles, tubo-eruptive and planar xanthomas, corneal arcus and opacification, no evidence of fat malabsorption, normal triglyceride levels, and premature coronary atherosclerosis, and 2) there at least three separate and distinct HDL particles in plasma: apoA-I HDL, apoA-IV HDL, and apoE HDL, with apoA-I HDL being the predominant form of HDL.