title: POPC/apoA-I discs as a potent lipoprotein modulator in Tangier disease.
abstract: Tangier disease (TD) is a rare familial disorder with mutations in the ATP-binding cassette transporter A1 (ABCA1) gene. It results in extremely low levels of HDL cholesterol. Since TD is a genetic disorder, a therapeutic approach to TD has not been established. We report a typical case of TD with a homozygous novel point mutation in the ABCA1 gene by using genomic DNA sequencing. Primary monocyte-derived macrophages of blood from a patient with TD and normolipidemic subjects were compared for cholesterol efflux. The macrophages from the TD patient showed no apoA-I-mediated cholesterol efflux. In contrast, POPC/apoA-I discs were able to take up cholesterol from macrophages from both the TD and normolipidemic subject. Capillary isotachophoresis (cITP), which separates lipoprotein into subfractions according to electrophoretic mobility, was used to characterize plasma lipoprotein subfractions. Both slow-migrating HDL (sHDL) and slow-migrating LDL (sLDL; unmodified LDL) subfractions were extremely low in the patient with TD. After incubation of plasma from the TD patient with POPC/apoA-I discs, sHDL and sLDL subfractions rapidly appeared. In conclusion, POPC/apoA-I discs not only have beneficial effects on cholesterol efflux, but also have potential as a lipoprotein modulator in patients with TD.
authors.affiliation: Department of Neurology and Healthcare, Fukuoka University Hospital, 7-45-1 Nanakuma, Jonan-ku, 814-0180 Fukuoka, Japan. ueharay@fukuoka-u.ac.jp
authors.forename: Yoshinari
authors.initials: Y
authors.lastname: Uehara
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Tsuboi
authors.forename: Bo
authors.initials: B
authors.lastname: Zhang
authors.forename: Shin-ichiro
authors.initials: S
authors.lastname: Miura
authors.forename: Yasuhiko
authors.initials: Y
authors.lastname: Baba
authors.forename: Masa-aki
authors.initials: MA
authors.lastname: Higuchi
authors.forename: Tatsuo
authors.initials: T
authors.lastname: Yamada
authors.forename: Kerry-Anne
authors.initials: KA
authors.lastname: Rye
authors.forename: Keijiro
authors.initials: K
authors.lastname: Saku
mesh_terms: D064286:ATP Binding Cassette Transporter 1; D018528:ATP-Binding Cassette Transporters / Q000235:genetics; D016632:Apolipoprotein A-I / Q000494:pharmacology*; D001055:Apolipoproteins B / Q000378:metabolism; D001057:Apolipoproteins E / Q000378:metabolism; D002478:Cells, Cultured; D002788:Cholesterol Esters / Q000378:metabolism; D008076:Cholesterol, HDL / Q000172:deficiency / Q000378:metabolism; D004586:Electrophoresis; D006801:Humans; D008264:Macrophages / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D010713:Phosphatidylcholines / Q000494:pharmacology*; D013631:Tangier Disease / Q000235:genetics / Q000378:metabolism*; D014280:Triglycerides / Q000378:metabolism
chemical_list: C577836:ABCA1 protein, human; D064286:ATP Binding Cassette Transporter 1; D018528:ATP-Binding Cassette Transporters; D016632:Apolipoprotein A-I; D001055:Apolipoproteins B; D001057:Apolipoproteins E; D002788:Cholesterol Esters; D008076:Cholesterol, HDL; D010713:Phosphatidylcholines; D014280:Triglycerides; C028694:1-palmitoyl-2-oleoylphosphatidylcholine