title: 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).
  
  
  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.
  
  
  CONCLUSIONS
  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.affiliation: Department of Internal Medicine and Medical Specialties, University of Palermo, Via del Vespro 141, I-90127 Palermo, Italy.
authors.forename: Davide
authors.initials: D
authors.lastname: Noto
authors.forename: Angelo B
authors.initials: AB
authors.lastname: Cefalù
authors.forename: Vincenza
authors.initials: V
authors.lastname: Valenti
authors.forename: Francesca
authors.initials: F
authors.lastname: Fayer
authors.forename: Elisa
authors.initials: E
authors.lastname: Pinotti
authors.forename: Mariangela
authors.initials: M
authors.lastname: Ditta
authors.forename: Rossella
authors.initials: R
authors.lastname: Spina
authors.forename: Giovanni
authors.initials: G
authors.lastname: Vigna
authors.forename: Pin
authors.initials: P
authors.lastname: Yue
authors.forename: Sekar
authors.initials: S
authors.lastname: Kathiresan
authors.forename: Patrizia
authors.initials: P
authors.lastname: Tarugi
authors.forename: Maurizio R
authors.initials: MR
authors.lastname: Averna
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000595:Amino Acid Sequence; D000091303:Angiopoietin-Like Protein 3; D000075802:Angiopoietin-like Proteins; D042682:Angiopoietins / Q000235:genetics*; D001055:Apolipoproteins B / Q000235:genetics*; D015415:Biomarkers / Q000097:blood; D002784:Cholesterol / Q000097:blood; D008076:Cholesterol, HDL / Q000097:blood; D018389:Codon, Nonsense; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D006995:Hypobetalipoproteinemias / Q000097:blood / Q000453:epidemiology / Q000235:genetics*; D007558:Italy / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D008923:Missouri / Q000453:epidemiology; D008969:Molecular Sequence Data; D020125:Mutation, Missense; D010641:Phenotype; D015995:Prevalence; D012720:Severity of Illness Index; D055815:Young Adult
chemical_list: C479896:ANGPTL3 protein, human; D000091303:Angiopoietin-Like Protein 3; D000075802:Angiopoietin-like Proteins; D042682:Angiopoietins; D001055:Apolipoproteins B; D015415:Biomarkers; D008076:Cholesterol, HDL; D018389:Codon, Nonsense; D002784:Cholesterol