title: Familial combined hyperlipidemia is associated with alterations in the cholesterol synthesis pathway.
abstract: OBJECTIVE
  Familial combined hyperlipidemia (FCH) is a common familial lipid disorder characterized by increases in plasma total cholesterol, triglyceride, and apolipoprotein B-100 levels. In light of prior metabolic and genetic research, our purpose was to ascertain whether FCH cases had significant abnormalities of plasma markers of cholesterol synthesis and absorption as compared to unaffected kindred members.
  
  
  RESULTS
  Plasma levels of squalene, desmosterol, and lathosterol (cholesterol synthesis markers) and campesterol, sitosterol, and cholestanol (cholesterol absorption markers) were measured by gas-liquid chromatography in 103 FCH patients and 240 normolipidemic relatives (NLR). Squalene, desmosterol, and lathosterol levels were 6% (0.078), 31%, (P<0.001) and 51% (P<0.001) higher in FCH as compared to NLR, and these differences were especially pronounced in women. An interaction with obesity was also noted for a subset of these markers. We did not observe any apparent differences for the cholesterol absorption markers among FCH patients and NLR.
  
  
  CONCLUSIONS
  Our data indicate that both men and women with FCH have alterations in the cholesterol synthesis pathway, resulting in 51% higher levels of lathosterol (and additionally desmosterol in women). Plasma levels of the cholesterol precursor sterol squalene were only slightly increased (6%), suggesting enhanced conversion of squalene to lathosterol in this disorder.
authors.affiliation: Lipid Metabolism Laboratory, Tufts University, 711 Washington Street, Boston, MA 02111-1524, USA. thomas.vanhimbergen@tufts.edu
authors.forename: Thomas M
authors.initials: TM
authors.lastname: van Himbergen
authors.forename: Seiko
authors.initials: S
authors.lastname: Otokozawa
authors.forename: Nirupa R
authors.initials: NR
authors.lastname: Matthan
authors.forename: Ernst J
authors.initials: EJ
authors.lastname: Schaefer
authors.forename: Aaron
authors.initials: A
authors.lastname: Buchsbaum
authors.forename: Masumi
authors.initials: M
authors.lastname: Ai
authors.forename: Lambertus J H
authors.initials: LJ
authors.lastname: van Tits
authors.forename: Jacqueline
authors.initials: J
authors.lastname: de Graaf
authors.forename: Anton F H
authors.initials: AF
authors.lastname: Stalenhoef
mesh_terms: D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000097:blood*; D004083:Cholestanol / Q000097:blood; D002784:Cholesterol / Q000031:analogs & derivatives / Q000096:biosynthesis* / Q000097:blood*; D003897:Desmosterol / Q000097:blood; D005260:Female; D006801:Humans; D006950:Hyperlipidemia, Familial Combined / Q000378:metabolism*; D007408:Intestinal Absorption / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D010840:Phytosterols / Q000097:blood; D012727:Sex Characteristics; D012855:Sitosterols / Q000097:blood; D013185:Squalene / Q000097:blood
chemical_list: D015415:Biomarkers; D010840:Phytosterols; D012855:Sitosterols; D003897:Desmosterol; C021273:campesterol; C025473:gamma-sitosterol; D013185:Squalene; C001521:lathosterol; D004083:Cholestanol; D002784:Cholesterol