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: Takeyoshi Murano, Takashi Yamaguchi, Ichiro Tatsuno, Masayo Suzuki, Hirofumi Noike, Tarou Takanami, Tomoe Yoshida, Mitsuya Suzuki, Ryuya Hashimoto, Takatoshi Maeno, Kensuke Terai, Wataru Tokuyama, Nobuyuki Hiruta, Wolfgang J Schneider, Hideaki Bujo
• Journal: Clinica chimica acta; international journal of clinical chemistry (Clin Chim Acta) Vol. 452 Pg. 167-72 (Jan 15 2016) ISSN: 1873-3492 [Electronic] Netherlands
• PMID: 26616730 (Publication Type: Case Reports, Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2015 Elsevier B.V. All rights reserved.

Chemical References

• ABCA1 protein, human
• ATP Binding Cassette Transporter 1
• Lipoproteins

Topics

• ATP Binding Cassette Transporter 1 (genetics)
• Adolescent
• Chromatography, Gel
• Chromatography, High Pressure Liquid
• Humans
• Lipoproteins (blood)
• Male
• Mutation
• Tangier Disease (blood, genetics)