6533b854fe1ef96bd12aec8b
RESEARCH PRODUCT
Prevalence of ANGPTL3 and APOB gene mutations in subjects with combined hypolipidemia.
Mariangela DittaPin YueGiovanni Battista VignaElisa PinottiAngelo B. CefalùPatrizia TarugiFrancesca FayerSekar KathiresanRossella SpinaVincenza ValentiMaurizio AvernaDavide Notosubject
MaleSettore MED/09 - Medicina InternaApolipoprotein BGene mutationCompound heterozygositymedicine.disease_causeSeverity of Illness IndexHypobetalipoproteinemiaschemistry.chemical_compoundGene Frequency80 and overPrevalenceMissense mutationgeneticsepidemiology; genetics; hypobetalipoproteinemia; lipoproteins; Adolescent; Adult; Aged; Aged 80 and over; Amino Acid Sequence; Angiopoietins; Apolipoproteins B; Biomarkers; Cholesterol; Cholesterol HDL; Female; Gene Frequency; Genetic Predisposition to Disease; Heterozygote; Homozygote; Humans; Hypobetalipoproteinemias; Italy; Male; Middle Aged; Missouri; Molecular Sequence Data; Phenotype; Prevalence; Severity of Illness Index; Young Adult; Codon Nonsense; Mutation Missense; Cardiology and Cardiovascular MedicineAged 80 and overMutationHomozygotehypobetalipoproteinemiaMiddle AgedCholesterolPhenotypeItalyCodon NonsenseepidemiologyFemaleCardiology and Cardiovascular MedicineHumanAdultmedicine.medical_specialtyHeterozygoteHDLAdolescentMolecular Sequence DataMutation MissenseSocio-culturaleAngiopoietinepidemiology; lipoproteins; genetics; hypobetalipoproteinemiaBiologyYoung AdultInternal medicinemedicineHumansGenetic Predisposition to DiseaseAmino Acid SequenceCodonAllele frequencyAgedAngiopoietin-Like Protein 3Apolipoproteins BMissouriCholesterolCholesterol HDLmedicine.diseaselipoproteinsEndocrinologyAngiopoietin-like ProteinsNonsensechemistryBiological MarkerMutationbiology.proteinHypobetalipoproteinemiaMissenseAngiopoietinsBiomarkersdescription
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.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2012-01-01 | Arteriosclerosis, thrombosis, and vascular biology |