Genetic and Biochemical Analyses in Dyslipidemic Patients Undergoing LDL Apheresis

Leslie J. Donato, Amy K. Saenger, Laura J. Train, Katrina E. Kotzer, Susan A. Lagerstedt, Jean M. Hornseth, Ananda Basu, Jeffrey L. Winters, Linnea M. Baudhuin

Research output: Contribution to journalArticlepeer-review

4 Scopus citations


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. Design: 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. Conclusion: 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.

Original languageEnglish (US)
Pages (from-to)256-265
Number of pages10
JournalJournal of Clinical Apheresis
Issue number5
StatePublished - Oct 1 2014


  • Dyslipidemia
  • Familial hypercholesterolemia
  • LDL apheresis
  • LDLR
  • Lipoproteins

ASJC Scopus subject areas

  • Hematology


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