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.