title: Biomarkers of cholesterol homeostasis in a clinical laboratory database sample comprising 667,718 patients.
abstract: BACKGROUND
  Circulating noncholesterol sterols/stanols (NCS) are used in clinical lipidology as surrogate measures of cholesterol synthesis and absorption, where they can be valuable tools in assessing cholesterol metabolism and personalizing therapies in patients with dyslipidemia.
  
  
  OBJECTIVE
  To describe the distributions of plasma NCS concentrations and inter-NCS correlations in a large cohort of American patients constituting a clinical laboratory database, and to investigate the relationship between circulating NCS, age, sex, and apolipoprotein E (APOE) genotype.
  
  
  METHODS
  A total of 667,718 patient blood samples submitted for testing to Health Diagnostic Laboratory, Inc. (Richmond, VA) were analyzed for cholesterol absorption markers (sitosterol, campesterol, and cholestanol) and one cholesterol synthesis marker (desmosterol). NCS percentiles were determined, along with intermarker correlations (Pearson's R). Analysis of variance was used to assess the effect of age and sex on NCS level, and to evaluate the relationship between cholesterol synthesis/absorption status and APOE genotype in a subset of 336,866 patients.
  
  
  RESULTS
  Mean NCS concentrations were: sitosterol, 2.45 μg/mL; campesterol, 3.3 μg/mL; cholestanol, 2.92 μg/mL; and desmosterol 0.99 μg/mL. The correlations between each NCS and its ratio to total cholesterol ranged from 0.72 (cholestanol) to 0.94 (desmosterol). NCS levels were significantly affected by age and sex (P < .0001), and prevalence of cholesterol hyperabsorption was higher in APOE ε4 allele carriers compared with the other APOE genotypes.
  
  
  CONCLUSIONS
  We have described sample distributions of NCS biomarkers and characterized their relationship to age, sex, and APOE genotype. These data may facilitate research into altered cholesterol homeostasis and human disease, and help physicians optimize lipid-lowering therapies.
authors.affiliation: Clinical Education Department, Foundation for Health Improvement and Technology (FHIT), Richmond, VA, USA; Clinical Affairs Department, Health Diagnostic Laboratory, Inc., Richmond, VA, USA. Electronic address: tdayspring@aol.com.
authors.forename: Thomas D
authors.initials: TD
authors.lastname: Dayspring
authors.affiliation: Clinical Affairs Department, Health Diagnostic Laboratory, Inc., Richmond, VA, USA.
authors.forename: Stephen A
authors.initials: SA
authors.lastname: Varvel
authors.affiliation: Clinical Affairs Department, Health Diagnostic Laboratory, Inc., Richmond, VA, USA.
authors.forename: Leila
authors.initials: L
authors.lastname: Ghaedi
authors.affiliation: Clinical Affairs Department, Health Diagnostic Laboratory, Inc., Richmond, VA, USA.
authors.forename: Dawn L
authors.initials: DL
authors.lastname: Thiselton
authors.affiliation: Clinical Affairs Department, Health Diagnostic Laboratory, Inc., Richmond, VA, USA.
authors.forename: James
authors.initials: J
authors.lastname: Bruton
authors.affiliation: Clinical Affairs Department, Health Diagnostic Laboratory, Inc., Richmond, VA, USA.
authors.forename: Joseph P
authors.initials: JP
authors.lastname: McConnell
mesh_terms: D000375:Aging / Q000097:blood; D001057:Apolipoproteins E / Q000235:genetics; D015415:Biomarkers / Q000097:blood*; D004083:Cholestanol / Q000097:blood / Q000378:metabolism*; D016208:Databases, Factual; D050171:Dyslipidemias / Q000097:blood / Q000235:genetics; D005260:Female; D005838:Genotype; D006706:Homeostasis; D006801:Humans; D007753:Laboratories; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D012727:Sex Characteristics
chemical_list: D001057:Apolipoproteins E; D015415:Biomarkers; D004083:Cholestanol
keywords: APOE genotype; Campesterol; Cholestanol; Cholesterol homeostasis; Desmosterol; Sitosterol