title: Subfraction analysis of circulating lipoproteins in a patient with Tangier disease due to a novel ABCA1 mutation.
abstract: Tangier disease, characterized by low or absent high-density lipoprotein (HDL), is a rare hereditary lipid storage disorder associated with frequent, but not obligatory, severe premature atherosclerosis due to disturbed reverse cholesterol transport from tissues. The reasons for the heterogeneity in atherogenicity in certain dyslipidemias have not been fully elucidated. Here, using high-performance liquid chromatography with a gel filtration column (HPLC-GFC), we have studied the lipoprotein profile of a 17-year old male patient with Tangier disease who to date has not developed manifest coronary atherosclerosis. The patient was shown to be homozygous for a novel mutation (Leu1097Pro) in the central cytoplasmic region of ATP-binding cassette transporter A1 (ABCA1). Serum total and HDL-cholesterol levels were 59mg/dl and 2mg/dl, respectively. Lipoprotein electrophoretic analyses on agarose and polyacrylamide gels showed the presence of massively abnormal lipoproteins. Further analysis by HPLC-GFC identified significant amounts of lipoproteins in low-density lipoprotein (LDL) subfractions. The lipoprotein particles found in the peak subfraction were smaller than normal LDL, were rich in triglycerides, but poor in cholesterol and phospholipids. These findings in an adolescent Tangier patient suggest that patients in whom these triglyceride-rich, cholesterol- and phospholipid-poor LDL-type particles accumulate over time, would experience an increased propensity for developing atherosclerosis.
authors.affiliation: Department of Clinical-Laboratory and Experimental-Research Medicine, Toho University Sakura Medical Center, Sakura, Japan.
authors.forename: Takeyoshi
authors.initials: T
authors.lastname: Murano
authors.affiliation: Center of Diabetes, Endocrinology and Metabolism, Toho University Sakura Medical Center, Sakura, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Yamaguchi
authors.affiliation: Center of Diabetes, Endocrinology and Metabolism, Toho University Sakura Medical Center, Sakura, Japan.
authors.forename: Ichiro
authors.initials: I
authors.lastname: Tatsuno
authors.affiliation: Cardiovascular Center, Toho University Sakura Medical Center, Sakura, Japan.
authors.forename: Masayo
authors.initials: M
authors.lastname: Suzuki
authors.affiliation: Cardiovascular Center, Toho University Sakura Medical Center, Sakura, Japan.
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Noike
authors.affiliation: Department of Otorhinolaryngology, Toho University Sakura Medical Center, Sakura, Japan.
authors.forename: Tarou
authors.initials: T
authors.lastname: Takanami
authors.affiliation: Department of Otorhinolaryngology, Toho University Sakura Medical Center, Sakura, Japan.
authors.forename: Tomoe
authors.initials: T
authors.lastname: Yoshida
authors.affiliation: Department of Otorhinolaryngology, Toho University Sakura Medical Center, Sakura, Japan.
authors.forename: Mitsuya
authors.initials: M
authors.lastname: Suzuki
authors.affiliation: Department of Ophthalmology, Toho University Sakura Medical Center, Sakura, Japan.
authors.forename: Ryuya
authors.initials: R
authors.lastname: Hashimoto
authors.affiliation: Department of Ophthalmology, Toho University Sakura Medical Center, Sakura, Japan.
authors.forename: Takatoshi
authors.initials: T
authors.lastname: Maeno
authors.affiliation: Department of Clinical-Laboratory and Experimental-Research Medicine, Toho University Sakura Medical Center, Sakura, Japan; Department of Pathology, Toho University Sakura Medical Center, Sakura, Japan.
authors.forename: Kensuke
authors.initials: K
authors.lastname: Terai
authors.affiliation: Department of Pathology, Toho University Sakura Medical Center, Sakura, Japan.
authors.forename: Wataru
authors.initials: W
authors.lastname: Tokuyama
authors.affiliation: Department of Clinical-Laboratory and Experimental-Research Medicine, Toho University Sakura Medical Center, Sakura, Japan; Department of Pathology, Toho University Sakura Medical Center, Sakura, Japan.
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Hiruta
authors.affiliation: Department of Medical Biochemistry, Max F. Perutz Laboratories, Medical University of Vienna, Vienna, Austria.
authors.forename: Wolfgang J
authors.initials: WJ
authors.lastname: Schneider
authors.affiliation: Department of Clinical-Laboratory and Experimental-Research Medicine, Toho University Sakura Medical Center, Sakura, Japan. Electronic address: hideaki.bujo@med.toho-u.ac.jp.
authors.forename: Hideaki
authors.initials: H
authors.lastname: Bujo
mesh_terms: D064286:ATP Binding Cassette Transporter 1 / Q000235:genetics*; D000293:Adolescent; D002850:Chromatography, Gel; D002851:Chromatography, High Pressure Liquid; D006801:Humans; D008074:Lipoproteins / Q000097:blood*; D008297:Male; D009154:Mutation; D013631:Tangier Disease / Q000097:blood* / Q000235:genetics*
chemical_list: C577836:ABCA1 protein, human; D064286:ATP Binding Cassette Transporter 1; D008074:Lipoproteins
keywords: ABCA1; HPLC-GFC; Small, triglyceride-rich LDL; Tangier disease