title: Genetic and biochemical analyses in dyslipidemic patients undergoing LDL apheresis.
abstract: OBJECTIVE
  Familial hypercholesterolemia (FH) can be due to mutations in LDLR, PCSK9, and APOB. In phenotypically defined patients, a subset remains unresponsive to lipid-lowering therapies and requires low density-lipoprotein (LDL) apheresis treatment. In this pilot study, we examined the genotype/phenotype relationship in patients with dyslipidemia undergoing routine LDL apheresis.
  
  
  METHODS
  LDLR, APOB, and PCKS9 were analyzed for disease-causing mutations in seven patients undergoing routine LDL apheresis. Plasma and serum specimens were collected pre- and post-apheresis and analyzed for lipid concentrations, Lp(a) cholesterol, and lipoprotein particle concentrations (via NMR).
  
  
  RESULTS
  We found that four patients harbored LDLR mutations and of these, three presented with xanthomas. While similar reductions in LDL-cholesterol (LDL-C), apolipoprotein B, and LDL particles (LDL-P) were observed following apheresis in all patients, lipid profile analysis revealed the LDLR mutation-positive cohort had a more pro-atherogenic profile (higher LDL-C, apolipoprotein B, LDL-P, and small LDL-P) pre-apheresis.
  
  
  CONCLUSIONS
  Our data show that not all clinically diagnosed FH patients who require routine apheresis have genetically defined disease. In our small cohort, those with LDLR mutations had a more proatherogenic phenotype than those without identifiable mutations. This pilot cohort suggests that patients receiving the maximum lipid lowering therapy could be further stratified, based on genetic make-up, to optimize treatment.
authors.affiliation: Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota.
authors.forename: Leslie J
authors.initials: LJ
authors.lastname: Donato
authors.forename: Amy K
authors.initials: AK
authors.lastname: Saenger
authors.forename: Laura J
authors.initials: LJ
authors.lastname: Train
authors.forename: Katrina E
authors.initials: KE
authors.lastname: Kotzer
authors.forename: Susan A
authors.initials: SA
authors.lastname: Lagerstedt
authors.forename: Jean M
authors.initials: JM
authors.lastname: Hornseth
authors.forename: Ananda
authors.initials: A
authors.lastname: Basu
authors.forename: Jeffrey L
authors.initials: JL
authors.lastname: Winters
authors.forename: Linnea M
authors.initials: LM
authors.lastname: Baudhuin
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D001781:Blood Component Removal; D008078:Cholesterol, LDL / Q000097:blood / Q000302:isolation & purification*; D005260:Female; D006801:Humans; D006938:Hyperlipoproteinemia Type II / Q000097:blood / Q000235:genetics / Q000628:therapy*; D017270:Lipoprotein(a) / Q000097:blood; D008297:Male; D008875:Middle Aged; D009154:Mutation; D011973:Receptors, LDL / Q000235:genetics
chemical_list: D008078:Cholesterol, LDL; D017270:Lipoprotein(a); D011973:Receptors, LDL
keywords: LDL apheresis; LDLR; dyslipidemia; familial hypercholesterolemia; lipoproteins