Bodzioch, Marek and Orso, Evelyn and Klucken, Jochen and Langmann, Thomas and Boettcher, Alfred and Diederich, Wendy and Drobnik, Wolfgang and Barlage, Stefan and Buechler, Christa and Porsch-Özcürümez, Mustafa and Kaminski, Wolfgang E. and Hahmann, Harry W. and Oette, Kurt and Rothe, Gregor and Aslanidis, Charalampos and Lackner, Karl J. and Schmitz, Gerd (1999) The gene encoding ATP-binding cassette transporter 1 is mutated in Tangier disease. NATURE GENETICS, 22 (4). pp. 347-351. ISSN 1061-4036,
Full text not available from this repository. (Request a copy)Abstract
Tangier disease (TD) is an autosomal recessive disorder of lipid metabolism(1). It is characterized by absence of plasma high-density lipoprotein (HDL) and deposition of cholesteryl esters in the reticulo-endothelial system with splenomegaly and enlargement of tonsils and lymph nodes(.)(2) Although low HDL cholesterol is associated with an increased risk for coronary artery disease, this condition is not consistently found in TD pedigrees. Metabolic studies in TD patients have revealed a rapid catabolism of HDL and its precursors(2). In contrast to normal mononuclear phagocytes (MNP), MNP from TD individuals degrade internalized HDL in unusual lysosomes, indicating a defect in cellular lipid metabolism(3,4). HDL-mediated cholesterol efflux and intracellular lipid trafficking and turnover are abnormal in TD fibroblasts(5-7), which have a reduced in vitro growth rates. The TD locus has been mapped to chromosome 9q31 (ref. 9). Here we present evidence that TD is caused by mutations in ABC1, encoding a member of the ATP-binding cassette (ABC) transporter family, located on chromosome 9q22-31 (ref. 10), We have analysed five kindreds with TD and identified seven different mutations, including three that are expected to impair the function of the gene product. The identification of ABC1 as the TD locus has implications for the understanding of cellular HDL metabolism and reverse cholesterol transport, and its association with premature cardiovascular disease.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | APOLIPOPROTEIN-A-I; CELLULAR CHOLESTEROL; ABC TRANSPORTERS; PHOSPHOLIPIDS; FIBROBLASTS; RECEPTOR; EFFLUX; |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Klinische Chemie und Laboratoriumsmedizin |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 11 Jan 2023 15:06 |
| Last Modified: | 11 Jan 2023 15:06 |
| URI: | https://pred.uni-regensburg.de/id/eprint/49100 |
Actions (login required)
 |
View Item |
