Abstract |
Defects in the gene encoding for the ATP binding cassette ( ABC) transporter A1 (ABCA1) were shown to be one of the genetic causes for familial hypoalphalipoproteinemia (FHA). We investigated the role of ABCA1-mediated cholesterol efflux in Dutch subjects suffering from FHA. Eighty-eight subjects (mean HDL cholesterol levels 0.63 +/- 0.21 mmol/l) were enrolled. Fibroblasts were cultured and loaded with [3H] cholesterol. ABCA1 and non-ABCA1-mediated efflux was studied by using apolipoprotein A-I ( apoA-I), HDL, and methyl-beta-cyclodextrin as acceptors. Efflux to apoA-I was decreased in four patients (4/88, 4.5%), and in all cases, a mutation in the ABCA1 gene was found. In the remaining 84 subjects, no correlation between efflux and apoA-I or HDL cholesterol was found. Efflux to both HDL and cyclodextrin, in contrast, did correlate with HDL cholesterol plasma levels (r = 0.34, P = 0.01; and r = 0.27, P = 0.008, respectively). The prevalence of defects in ABCA1-dependent cholesterol efflux in Dutch FHA patients is low. The significant correlation between plasma HDL cholesterol levels and methyl-beta-cyclodextrin-mediated efflux in the FHA patients with normal ABCA1 function suggests that non-ABCA1-mediated efflux might also be important for plasma HDL cholesterol levels in these individuals.
|
Authors | G Kees Hovingh, Michel J A Van Wijland, Alison Brownlie, Radjesh J Bisoendial, Michael R Hayden, John J P Kastelein, Albert K Groen |
Journal | Journal of lipid research
(J Lipid Res)
Vol. 44
Issue 6
Pg. 1251-5
(Jun 2003)
ISSN: 0022-2275 [Print] United States |
PMID | 12700344
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
|
Chemical References |
- ABCA1 protein, human
- ATP Binding Cassette Transporter 1
- ATP-Binding Cassette Transporters
- Apolipoprotein A-I
- Cholesterol, HDL
- Cholesterol, LDL
- Cyclodextrins
- Triglycerides
- beta-Cyclodextrins
- methyl-beta-cyclodextrin
- Cholesterol
|
Topics |
- ATP Binding Cassette Transporter 1
- ATP-Binding Cassette Transporters
(genetics, metabolism)
- Aged
- Apolipoprotein A-I
(metabolism)
- Cholesterol
(metabolism)
- Cholesterol, HDL
(blood, metabolism)
- Cholesterol, LDL
(blood, metabolism)
- Cyclodextrins
(metabolism)
- Fibroblasts
(metabolism)
- Humans
- Middle Aged
- Mutation
- Tangier Disease
(blood, genetics, metabolism)
- Triglycerides
(metabolism)
- beta-Cyclodextrins
|