title: Increased intestinal cholesterol absorption in autosomal dominant hypercholesterolemia and no mutations in the low-density lipoprotein receptor or apolipoprotein B genes.
abstract: BACKGROUND
  Autosomal dominant hypercholesterolemia (ADH) is frequently caused by functional mutations in the low-density lipoprotein receptor (LDLR) or apolipoprotein B-100 (APOB) genes, but approximately 40% of ADH subjects disclose no such molecular defects, possibly pointing to alternative genetic mechanisms.
  
  
  OBJECTIVE
  Our objective was to test the hypothesis that increased intestinal cholesterol absorption might play a role in the lipid abnormalities of subjects with ADH without identified genetic defects.
  
  
  METHODS
  This is a cross-sectional study of consecutive subjects with primary hyperlipidemia identified during an 18-month period in two lipid clinics.
  
  
  METHODS
  A total of 52 subjects with a clinical diagnosis of ADH were examined for molecular defects in LDLR and APOB. No APOB defects were found. Functional LDLR mutations occurred in 31 (60%) subjects, who received a diagnosis of familial hypercholesterolemia (FH). Those for whom no mutations could be identified were labeled as non-FH ADH. In addition, 38 subjects with familial combined hyperlipidemia (FCH) and 45 normolipidemic control subjects were studied.
  
  
  METHODS
  Interventions were diagnostic.
  
  
  METHODS
  Serum noncholesterol sterols were used as markers for the efficiency of intestinal cholesterol absorption.
  
  
  RESULTS
  Adjusted campesterol to cholesterol ratios increased in the order non-FH ADH more than FH more than controls more than FCH, with mean values (95% confidence interval) in 10(2) mmol/mol cholesterol of 505 (424-600), 397 (345-458), 335 (294-382), and 284 (247-328), respectively. Thus, cholesterol absorption was lowest in FCH and highest in non-FH ADH.
  
  
  CONCLUSIONS
  Increased intestinal cholesterol absorption may partially explain the high cholesterol levels of non-FH ADH subjects. Serum noncholesterol sterols are a useful tool for the differential diagnosis of genetic hypercholesterolemias, especially FCH and ADH unrelated to LDLR or APOB defects.
authors.affiliation: Laboratorio de Investigación Molecular, Hospital Universitario Miguel Servet, Instituto Aragonés de Ciencias de la Salud (I+CS), Po Isabel la Católica, 1-3, 50009 Zaragoza, Spain. algarcia.iacs@aragon.es
authors.forename: A L
authors.initials: AL
authors.lastname: García-Otín
authors.forename: M
authors.initials: M
authors.lastname: Cofán
authors.forename: M
authors.initials: M
authors.lastname: Junyent
authors.forename: D
authors.initials: D
authors.lastname: Recalde
authors.forename: A
authors.initials: A
authors.lastname: Cenarro
authors.forename: M
authors.initials: M
authors.lastname: Pocoví
authors.forename: E
authors.initials: E
authors.lastname: Ros
authors.forename: F
authors.initials: F
authors.lastname: Civeira
mesh_terms: D000328:Adult; D001055:Apolipoproteins B / Q000235:genetics*; D002784:Cholesterol / Q000378:metabolism*; D003430:Cross-Sectional Studies; D004252:DNA Mutational Analysis; D005260:Female; D006801:Humans; D006938:Hyperlipoproteinemia Type II / Q000235:genetics* / Q000378:metabolism*; D007408:Intestinal Absorption / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D011973:Receptors, LDL / Q000235:genetics*; D013261:Sterols / Q000378:metabolism
chemical_list: D001055:Apolipoproteins B; D011973:Receptors, LDL; D013261:Sterols; D002784:Cholesterol