Abstract | OBJECTIVE: Mutations of the ANGPTL3 gene have been associated with a novel form of primary hypobetalipoproteinemia, the combined hypolipidemia (cHLP), characterized by low total cholesterol and low HDL-cholesterol levels. The aim of this work is to define the role of ANGPTL3 gene as determinant of the combined hypolipidemia phenotype in 2 large cohorts of 913 among American and Italian subjects with primary hypobetalipoproteinemia (total cholesterol<5th percentile). METHODS AND RESULTS: The combined hypolipidemia cut-offs were chosen according to total cholesterol and HDL-cholesterol levels reported in the ANGPTL3 kindred described to date: total cholesterol levels, <2nd percentile and HDL-cholesterol, levels<2nd decile. Seventy-eight subjects with combined hypolipidemia were analyzed for ANGPTL3 and APOB genes. We identified nonsense and/or missense mutations in ANGPTL3 gene in 8 subjects; no mutations of the APOB gene were found. Mutated ANGPTL3 homozygous/compound heterozygous subjects showed a more severe biochemical phenotype compared to heterozygous or ANGPTL3 negative subjects, although ANGPTL3 heterozygotes did not differ from ANGPTL3 negative subjects. CONCLUSION: These results demonstrated that in a cohort of subjects with severe primary hypobetalipoproteinemia the prevalence of ANGPTL3 gene mutations responsible for a combined hypolipidemia phenotype is about 10%, whereas mutations of APOB gene are absent.
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Authors | Davide Noto, Angelo B Cefalù, Vincenza Valenti, Francesca Fayer, Elisa Pinotti, Mariangela Ditta, Rossella Spina, Giovanni Vigna, Pin Yue, Sekar Kathiresan, Patrizia Tarugi, Maurizio R Averna |
Journal | Arteriosclerosis, thrombosis, and vascular biology
(Arterioscler Thromb Vasc Biol)
Vol. 32
Issue 3
Pg. 805-9
(Mar 2012)
ISSN: 1524-4636 [Electronic] United States |
PMID | 22247256
(Publication Type: Journal Article, Multicenter Study, Research Support, Non-U.S. Gov't)
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Chemical References |
- ANGPTL3 protein, human
- Angiopoietin-Like Protein 3
- Angiopoietin-like Proteins
- Angiopoietins
- Apolipoproteins B
- Biomarkers
- Cholesterol, HDL
- Codon, Nonsense
- Cholesterol
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Topics |
- Adolescent
- Adult
- Aged
- Aged, 80 and over
- Amino Acid Sequence
- Angiopoietin-Like Protein 3
- Angiopoietin-like Proteins
- Angiopoietins
(genetics)
- Apolipoproteins B
(genetics)
- Biomarkers
(blood)
- Cholesterol
(blood)
- Cholesterol, HDL
(blood)
- Codon, Nonsense
- Female
- Gene Frequency
- Genetic Predisposition to Disease
- Heterozygote
- Homozygote
- Humans
- Hypobetalipoproteinemias
(blood, epidemiology, genetics)
- Italy
(epidemiology)
- Male
- Middle Aged
- Missouri
(epidemiology)
- Molecular Sequence Data
- Mutation, Missense
- Phenotype
- Prevalence
- Severity of Illness Index
- Young Adult
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