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Titolo:
CHOLESTEROL-LOWERING DRUG-THERAPY IN A PATIENT WITH RECEPTOR-NEGATIVEHOMOZYGOUS FAMILIAL HYPERCHOLESTEROLEMIA
Autore:
FEHER MD; WEBB JC; PATEL DD; LANT AF; MAYNE PD; KNIGHT BL; SOUTAR AK;
Indirizzi:
HAMMERSMITH HOSP,MRC,LIPOPROT TEAM LONDON W12 0HS ENGLAND HAMMERSMITH HOSP,MRC,LIPOPROT TEAM LONDON W12 0HS ENGLAND CHELSEA & WESTMINSTER HOSP,DEPT ACAD THERAPEUT,LIPID CLIN LONDON SW109NH ENGLAND
Titolo Testata:
Atherosclerosis
fascicolo: 2, volume: 103, anno: 1993,
pagine: 171 - 180
SICI:
0021-9150(1993)103:2<171:CDIAPW>2.0.ZU;2-B
Fonte:
ISI
Lingua:
ENG
Soggetto:
LOW-DENSITY-LIPOPROTEIN; PRIMARY MODERATE HYPERCHOLESTEROLEMIA; CULTURED HUMAN-FIBROBLASTS; LDL RECEPTOR; CYTOPLASMIC DOMAIN; GENE; MUTATION; ASSOCIATION; METABOLISM; NONSENSE;
Keywords:
MUTATION; LDL RECEPTOR GENE; GENE AMPLIFICATION; POLYMORPHISM;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Citazioni:
32
Recensione:
Indirizzi per estratti:
Citazione:
M.D. Feher et al., "CHOLESTEROL-LOWERING DRUG-THERAPY IN A PATIENT WITH RECEPTOR-NEGATIVEHOMOZYGOUS FAMILIAL HYPERCHOLESTEROLEMIA", Atherosclerosis, 103(2), 1993, pp. 171-180

Abstract

Familial hypercholesterolaemia (FH) is caused by mutations in the gene for the low density lipoprotein (LDL) receptor. It is generally believed that homozygous FH patients do not respond well to lipid-loweringdrug therapy with inhibitors of 3-hydroxy-3-methylglutaryl CoA reductase because they cannot respond to an increased demand for hepatic cholesterol by up-regulation of LDL-receptor activity. In this paper we show that serum cholesterol in a homozygous FH patient with a receptor-negative LDL-receptor phenotype was reduced by 30% after treatment with simvastatin alone and by a further 11% with simvastatin in combination with probucol and nicotinic acid. The patient was a true homozygote, with two identical alleles of the LDL receptor gene in which a previously undescribed point mutation in exon 11 introduces a premature termination codon at residue 540 in the protein; the mutant protein is predicted to be truncated in the domain with homology to the epidermal growth factor precursor. Cultured cells from the patient were unable tobind, internalise or degrade LDL by the receptor pathway and there was no immunodetectable LDL receptor protein in the cells. Thus the lipid lowering effect of simvastatin in this individual must involve mechanisms other than stimulation of LDL receptors.

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Documento generato il 04/12/20 alle ore 12:58:03