Genetic etiology of isolated low HDL syndrome: incidence and heterogeneity of efflux defects.
Arterioscler Thromb Vasc Biol
; 27(5): 1139-45, 2007 May.
Article
em En
| MEDLINE
| ID: mdl-17303779
ABSTRACT
OBJECTIVE:
We have used a multitiered approach to identify genetic and cellular contributors to high-density lipoprotein (HDL) deficiency in 124 human subjects. METHODS ANDRESULTS:
We resequenced 4 candidate genes for HDL regulation and identified several functional nonsynonymous mutations including 2 in apolipoprotein A-I (APOA1), 4 in lecithincholesterol acyltransferase (LCAT), 1 in phospholipid transfer protein (PLTP), and 7 in the ATP-binding cassette transporter ABCA1, leaving 88% (110/124) of HDL deficient subjects without a genetic diagnosis. Cholesterol efflux assays performed using cholesterol-loaded monocyte-derived macrophages from the 124 low HDL subjects and 48 control subjects revealed that 33% (41/124) of low HDL subjects had low efflux, despite the fact that the majority of these subjects (34/41) were not carriers of dysfunctional ABCA1 alleles. In contrast, only 2% of control subjects presented with low efflux (1/48). In 3 families without ABCA1 mutations, efflux defects were found to cosegregate with low HDL.CONCLUSIONS:
Efflux defects are frequent in low HDL syndromes, but the majority of HDL deficient subjects with cellular cholesterol efflux defects do not harbor ABCA1 mutations, suggesting that novel pathways contribute to this phenotype.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
RNA
/
Apolipoproteína A-I
/
Hipercolesterolemia
/
HDL-Colesterol
/
Mutação
Tipo de estudo:
Etiology_studies
/
Incidence_studies
/
Risk_factors_studies
Limite:
Humans
/
Middle aged
Idioma:
En
Ano de publicação:
2007
Tipo de documento:
Article