title: Apolipoprotein composition of HDL in cholesteryl ester transfer protein deficiency.
abstract: Our purpose was to compare HDL subpopulations, as determined by nondenaturing two-dimensional gel electrophoresis followed by immunoblotting for apolipoprotein A-I (apoA-I), apoA-II, apoA-IV, apoCs, and apoE in heterozygous, compound heterozygous, and homozygous subjects for cholesteryl ester transfer protein (CETP) deficiency and controls. Heterozygotes, compound heterozygotes, and homozygotes had CETP masses that were 30, 63, and more than 90% lower and HDL-cholesterol values that were 64, 168, and 203% higher than those in controls, respectively. Heterozygotes had approximately 50% lower pre-beta-1 and more than 2-fold higher levels of alpha-1 and pre-alpha-1 particles than controls. Three of the five heterozygotes' alpha-1 particles also contained apoA-II, which was not seen in controls. Compound heterozygotes and homozygotes had very large particles not observed in controls and heterozygotes. These particles contained apoA-I, apoA-II, apoCs, and apoE. However, these subjects did not have decreased pre-beta-1 levels. Our data indicate that CETP deficiency results in the formation of very large HDL particles containing all of the major HDL apolipoproteins except for apoA-IV. We hypothesize that the HDL subpopulation profile of heterozygous CETP-deficient patients, especially those with high levels of alpha-1 containing apoA-I but no apoA-II, represent an improved anti-atherogenic state, although this might not be the case for compound heterozygotes and homozygotes with very large, undifferentiated HDL particles.
authors.affiliation: Lipid Metabolism Laboratory, Jean Mayer United States Department of Agriculture Human Nutrition Research Center on Aging, Tufts University, Boston, MA, USA. bela.asztalos@tufts.edu
authors.forename: Bela F
authors.initials: BF
authors.lastname: Asztalos
authors.forename: Katalin V
authors.initials: KV
authors.lastname: Horvath
authors.forename: Kouji
authors.initials: K
authors.lastname: Kajinami
authors.forename: Chorthip
authors.initials: C
authors.lastname: Nartsupha
authors.forename: Caitlin E
authors.initials: CE
authors.lastname: Cox
authors.forename: Marcelo
authors.initials: M
authors.lastname: Batista
authors.forename: Ernst J
authors.initials: EJ
authors.lastname: Schaefer
authors.forename: Akihiro
authors.initials: A
authors.lastname: Inazu
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Mabuchi
mesh_terms: D000328:Adult; D016632:Apolipoprotein A-I / Q000097:blood; D016633:Apolipoprotein A-II / Q000097:blood; D001053:Apolipoproteins / Q000032:analysis* / Q000737:chemistry; D001054:Apolipoproteins A / Q000097:blood; D015415:Biomarkers / Q000097:blood; D002352:Carrier Proteins; D053480:Cholesterol Ester Transfer Proteins; D005260:Female; D005838:Genotype; D006023:Glycoproteins / Q000172:deficiency*; D006801:Humans; D008075:Lipoproteins, HDL / Q000737:chemistry*; D008297:Male; D008661:Metabolism, Inborn Errors / Q000097:blood / Q000235:genetics* / Q000378:metabolism*; D008875:Middle Aged
chemical_list: D016632:Apolipoprotein A-I; D016633:Apolipoprotein A-II; D001053:Apolipoproteins; D001054:Apolipoproteins A; D015415:Biomarkers; C506642:CETP protein, human; D002352:Carrier Proteins; D053480:Cholesterol Ester Transfer Proteins; D006023:Glycoproteins; D008075:Lipoproteins, HDL; C022205:apolipoprotein A-IV