Genetics of Familial Hypercholesterolemia

Ariel Brautbar, Emili Leary, Kristen Rasmussen, Don P. Wilson, Robert D. Steiner, Salim Virani

Research output: Contribution to journalReview articlepeer-review

69 Citations (Scopus)


Familial hypercholesterolemia (FH) is a genetic disorder characterized by elevated low-density lipoprotein (LDL) cholesterol and premature cardiovascular disease, with a prevalence of approximately 1 in 200–500 for heterozygotes in North America and Europe. Monogenic FH is largely attributed to mutations in the LDLR, APOB, and PCSK9 genes. Differential diagnosis is critical to distinguish FH from conditions with phenotypically similar presentations to ensure appropriate therapeutic management and genetic counseling. Accurate diagnosis requires careful phenotyping based on clinical and biochemical presentation, validated by genetic testing. Recent investigations to discover additional genetic loci associated with extreme hypercholesterolemia using known FH families and population studies have met with limited success. Here, we provide a brief overview of the genetic determinants, differential diagnosis, genetic testing, and counseling of FH genetics.

Original languageEnglish
JournalCurrent Atherosclerosis Reports
Issue number4
Publication statusPublished - Apr 2015
Externally publishedYes


  • Apolipoprotein B (APOB)
  • Autosomal recessive hypercholesterolemia (ARH)
  • Cascade testing
  • Cerebrotendinous xanthomatosis (CTX)
  • Cholesterol ester storage disease (CESD)
  • Familial defective apolipoprotein B-100 (FDB)
  • Familial hypercholesterolemia (FH)
  • Genetic counseling (GC)
  • LDL receptor adapter protein 1 (LDLRAP1)
  • Low-density lipoprotein receptor (LDLR)
  • Penetrance
  • Proprotein convertase subtilisin/kexin type 9 (PCSK9)
  • Sitosterolemia


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