Prevalence of ANGPTL3 and APOB gene mutations in subjects with combined hypolipidemia.

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.

• 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)

Chemical References

• ANGPTL3 protein, human
• Angiopoietin-Like Protein 3
• Angiopoietin-like Proteins
• Angiopoietins
• Apolipoproteins B
• Biomarkers
• Cholesterol, HDL
• Codon, Nonsense
• Cholesterol

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