A novel nonsense apolipoprotein A-I mutation (apoA-I(E136X)) causes low HDL cholesterol in French Canadians.
Atherosclerosis
; 185(1): 127-36, 2006 Mar.
Article
em En
| MEDLINE
| ID: mdl-16023124
ABSTRACT
The molecular causes of severe high-density lipoprotein cholesterol (HDL-C) deficiency was examined in a group of 54 unrelated French Canadian subjects. The lecithincholesterol acyl transferase (LCAT) and apolipoprotein (apo) A-I gene were analyzed in all probands by direct DNA sequencing. While no LCAT mutation was detected, a novel nonsense apoA-I mutation (E136X) was found in 3/54 probands. Genetic analysis of two kindreds showed a strong co-segregation of the apoA-I locus with the low HDL-C trait. The E136X mutation was detected in families by MaeI restriction digestion. E136X carriers (n=17) had marked HDL-C deficiency; among the nine carriers > or = 35 years old, five men had developed premature coronary artery disease (CAD). A peptide of apparent molecular weight of 14 kDa was identified in fresh plasma, the HDL fractions and lipoprotein deficient plasma from the three probands but not in normal controls (n=3), suggesting that the mutant apoA-I peptide is secreted and binds lipids. The mutation was not observed in an additional 210 chromosomes from unrelated subjects of French Canadian descent, < 60 years of age, with CAD and low HDL-C levels. We conclude that apoA-I (E136X) is a cause of HDL-C deficiency in the French Canadian population and is associated with premature CAD.
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Base de dados:
MEDLINE
Assunto principal:
Doença de Tangier
/
DNA
/
Apolipoproteína A-I
/
Códon sem Sentido
/
HDL-Colesterol
Tipo de estudo:
Etiology_studies
Limite:
Adolescent
/
Adult
/
Aged
/
Child
/
Female
/
Humans
/
Male
/
Middle aged
País como assunto:
America do norte
/
Europa
Idioma:
En
Ano de publicação:
2006
Tipo de documento:
Article