title: Bile acid synthesis precursors in familial combined hyperlipidemia: the oxysterols 24S-hydroxycholesterol and 27-hydroxycholesterol.
abstract: Familial combined hyperlipidemia (FCHL), the most common inherited disorder of lipid metabolism is characterized by increasing cholesterol synthesis precursors due to hepatic overproduction of cholesterol. The bile acids synthesis pathway has not been previously studied in FCHL. The aim of this work was to study the oxysterol levels which are involved in the bile acids synthesis from cholesterol in FCHL. Clinical parameters and subclinical atherosclerosis were studied in a total of 107 FCHL patients and 126 normolipidemic controls. Non cholesterol sterols (desmosterol and lanosterol) and oxysterols (27-hydroxycholesterol and 24S-hydroxycholesterol) were measured by high performance liquid chromatography tandem mass spectrometry. Desmosterol and lanosterol, markers of cholesterol synthesis, had a positive correlation with BMI and apo B. However, no correlation was found for 24S-hydroxycholesterol and 27-hydroxycholesterol, precursors of bile acids, with these clinical parameters. Only 27-hydroxycholesterol had a positive correlation with apo B, ρ=0.204 (P=0.037). All oxysterol levels were higher in FHCL as compared to normal controls. A total of 59 FCHL subjects (59%) presented values of 24S-hydroxycholesterol above the 95th percentile of this oxysterol in the control population. All oxysterols showed no association with fat mass in contrast with non-cholesterol sterols. FCHL subjects with oxysterol overproduction had less carotid intima media thickness (cIMT), which suggests less atherosclerosis in these subjects. In summary, our data indicate that high oxysterol levels might be good markers of FCHL, unrelated to fat mass, and may exert a protective mechanism for cholesterol accumulation.
authors.affiliation: Unidad de Lípidos and Laboratorio de Investigación Molecular, Hospital Universitario Miguel Servet, Instituto Aragonés de Ciencias de la Salud (I+CS), Zaragoza, Spain. Electronic address: lbaila.iacs@aragon.es.
authors.forename: Lucía
authors.initials: L
authors.lastname: Baila-Rueda
authors.affiliation: Unidad de Lípidos and Laboratorio de Investigación Molecular, Hospital Universitario Miguel Servet, Instituto Aragonés de Ciencias de la Salud (I+CS), Zaragoza, Spain.
authors.forename: Rocío
authors.initials: R
authors.lastname: Mateo-Gallego
authors.affiliation: Unidad de Lípidos and Laboratorio de Investigación Molecular, Hospital Universitario Miguel Servet, Instituto Aragonés de Ciencias de la Salud (I+CS), Zaragoza, Spain.
authors.forename: Estibaliz
authors.initials: E
authors.lastname: Jarauta
authors.affiliation: Unidad de Lípidos and Laboratorio de Investigación Molecular, Hospital Universitario Miguel Servet, Instituto Aragonés de Ciencias de la Salud (I+CS), Zaragoza, Spain.
authors.forename: Isabel
authors.initials: I
authors.lastname: de Castro-Orós
authors.affiliation: Unidad de Lípidos and Laboratorio de Investigación Molecular, Hospital Universitario Miguel Servet, Instituto Aragonés de Ciencias de la Salud (I+CS), Zaragoza, Spain.
authors.forename: Ana M
authors.initials: AM
authors.lastname: Bea
authors.affiliation: Unidad de Lípidos and Laboratorio de Investigación Molecular, Hospital Universitario Miguel Servet, Instituto Aragonés de Ciencias de la Salud (I+CS), Zaragoza, Spain.
authors.forename: Ana
authors.initials: A
authors.lastname: Cenarro
authors.affiliation: Unidad de Lípidos and Laboratorio de Investigación Molecular, Hospital Universitario Miguel Servet, Instituto Aragonés de Ciencias de la Salud (I+CS), Zaragoza, Spain.
authors.forename: Fernando
authors.initials: F
authors.lastname: Civeira
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001647:Bile Acids and Salts / Q000096:biosynthesis; D015992:Body Mass Index; D059168:Carotid Intima-Media Thickness; D016022:Case-Control Studies; D003897:Desmosterol / Q000097:blood; D005260:Female; D006801:Humans; D006888:Hydroxycholesterols / Q000097:blood*; D006950:Hyperlipidemia, Familial Combined / Q000097:blood* / Q000000981:diagnostic imaging; D007810:Lanosterol / Q000097:blood; D008297:Male; D008875:Middle Aged; D055815:Young Adult
chemical_list: D001647:Bile Acids and Salts; D006888:Hydroxycholesterols; D007810:Lanosterol; D003897:Desmosterol; C044563:24-hydroxycholesterol; C076996:27-hydroxycholesterol
keywords: Cholesterol; Familial combined hypercholesterolemia; Non-cholesterol sterol; Oxysterol