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Titolo:
Mutations in the ABC1 gene in familial HDL deficiency with defective cholesterol efflux
Autore:
Marcil, M; Brooks-Wilson, A; Clee, SM; Roomp, K; Zhang, LH; Yu, L; Collins, JA; van Dam, M; Molhuizen, HOF; Loubster, O; Ouellette, BFF; Sensen, CW; Fichter, K; Mott, S; Denis, M; Boucher, B; Pimstone, S; Genest, J; Kastelein, JJP; Hayden, MR;
Indirizzi:
Xenon Biores Inc, NRC Innovat Ctr, Vancouver, BC, Canada Xenon Biores IncVancouver BC Canada Innovat Ctr, Vancouver, BC, Canada Univ British Columbia, Womens & Childrens Hosp, Ctr Mol Med & Therapeut, Vancouver, BC V5Z 1M9, Canada Univ British Columbia Vancouver BC Canada V5Z1M9 ver, BC V5Z 1M9, Canada Acad Med Ctr, Dept Vasc Med, NL-1005 AZ Amsterdam, Netherlands Acad Med Ctr Amsterdam Netherlands NL-1005 AZ AZ Amsterdam, Netherlands Clin Res Inst Montreal, Cardiovasc Genet Lab, Montreal, PQ H2W 1R7, CanadaClin Res Inst Montreal Montreal PQ Canada H2W 1R7 eal, PQ H2W 1R7, Canada NRC, Inst Marine Biosci, Halifax, NS, Canada NRC Halifax NS CanadaNRC, Inst Marine Biosci, Halifax, NS, Canada
Titolo Testata:
LANCET
fascicolo: 9187, volume: 354, anno: 1999,
pagine: 1341 - 1346
SICI:
0140-6736(19991016)354:9187<1341:MITAGI>2.0.ZU;2-R
Fonte:
ISI
Lingua:
ENG
Soggetto:
SUBSTRATE-SPECIFICITY; TANGIER-DISEASE; APOA-I; LIPOPROTEIN; HYPERCATABOLISM; TRANSPORTER; FIBROBLASTS; DYSTROPHY; POSITION; LIPASE;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Clinical Medicine
Life Sciences
Citazioni:
35
Recensione:
Indirizzi per estratti:
Indirizzo: Hayden, MR Ctr Mol Med & Therapeut, 950 W 28th Ave, Vancouver, BC V5Z 4H4,Canada Ctr Mol Med & Therapeut 950 W 28th Ave Vancouver BC Canada V5Z 4H4
Citazione:
M. Marcil et al., "Mutations in the ABC1 gene in familial HDL deficiency with defective cholesterol efflux", LANCET, 354(9187), 1999, pp. 1341-1346

Abstract

Background A low concentration of HDL cholesterol is the most common lipoprotein abnormality in patients with premature atherosclerosis. We have shown that Tangier disease, a rare and severe form of HDL deficiency characterised by a biochemical defect in cellular cholesterol efflux, is caused by mutations in the ATP-binding-cassette (ABC1) gene. This gene codes for the cholesterol-efflux regulatory protein (CERP). We investigated the presence ofmutations in this gene in patients with familiar HDL deficiency. Methods Three French-Canadian families and one Dutch family with familial HDL deficiency were studied. Fibroblasts from the proband of each family were defective in cellular cholesterol efflux. Genomic DNA of each proband was used for mutation detection with primers flanking each exon of the ABC1 gene, and for sequencing of the entire coding region of the gene. PCR and restriction-fragment length polymorphism assays specific to each mutation were used to investigate segregation of the mutation in each family, and to test for absence of the mutation in DNA from normal controls. Findings A different mutation was detected in ABC1 in each family studied. Each mutation either created a stop codon predicted to result in truncation of CERP, or altered a conserved aminoacid residue. Each mutation segregated with low concentrations of HDL-cholesterol in the family, and was not observed in more than 500 control chromosomes tested. Interpretation These data show that mutations in ABC1 are the major cause of familial HDL deficiency associated with defective cholesterol efflux, and that CERP has an essential role in the formation of HDL. Our findings highlight the potential of modulation of ABC1 as a new route for increasing HDL concentrations.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 29/03/20 alle ore 15:24:05