title: 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.affiliation: Lipid Clinic and Lipid Metabolism Laboratory, Heart Institute (InCor), University of Sao Paulo Medical School Hospital, Sao Paulo, Brazil. raul.santos@incor.usp.br
authors.forename: Raul D
authors.initials: RD
authors.lastname: Santos
authors.forename: Ernst J
authors.initials: EJ
authors.lastname: Schaefer
authors.forename: Bela F
authors.initials: BF
authors.lastname: Asztalos
authors.forename: Eliana
authors.initials: E
authors.lastname: Polisecki
authors.forename: Jian
authors.initials: J
authors.lastname: Wang
authors.forename: Robert A
authors.initials: RA
authors.lastname: Hegele
authors.forename: Lilton R C
authors.initials: LR
authors.lastname: Martinez
authors.forename: Marcio H
authors.initials: MH
authors.lastname: Miname
authors.forename: Carlos E
authors.initials: CE
authors.lastname: Rochitte
authors.forename: Protasio L
authors.initials: PL
authors.lastname: Da Luz
authors.forename: Raul C
authors.initials: RC
authors.lastname: Maranhão
mesh_terms: D000328:Adult; D000368:Aged; D016632:Apolipoprotein A-I / Q000097:blood / Q000172:deficiency* / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D008076:Cholesterol, HDL / Q000097:blood; D005260:Female; D006801:Humans; D007009:Hypolipoproteinemias / Q000097:blood / Q000235:genetics* / Q000378:metabolism*; D008075:Lipoproteins, HDL / Q000097:blood / Q000737:chemistry*; D008297:Male; D010316:Particle Size; D010375:Pedigree; D014973:Xanthomatosis / Q000378:metabolism
chemical_list: D016632:Apolipoprotein A-I; D008076:Cholesterol, HDL; D008075:Lipoproteins, HDL