Molecular genetic epidemiology of homozygous familial hypercholesterolemia in the Hokuriku district of Japan

Atherosclerosis. 2011 Feb;214(2):404-7. doi: 10.1016/j.atherosclerosis.2010.11.005. Epub 2010 Nov 13.


Aim: Familial hypercholesterolemia (FH) is caused by mutations of FH genes, i.e. LDL-receptor (LDLR), PCSK9 and apolipoprotein B (ApoB) gene. We evaluated the usefulness of DNA analysis for the diagnosis of homozygous FH (homo-FH), and studied the frequency of FH in the Hokuriku district of Japan.

Methods: Twenty-five homo-FH patients were recruited. LDLR mutations were identified using the Invader assay method. Mutations in PCSK9 were detected by PCR-SSCP followed by direct sequence analysis.

Results: We confirmed 15 true homozygotes and 10 compound heterozygotes for LDLR mutations. Three types of double heterozygotes for LDLR and PCSK9 were found. No FH patients due to ApoB mutations were found. The incidences of homo-FH and hetero-FH in the Hokuriku district were 1/171,167 and 1/208, respectively.

Conclusions: Our observations underlined the value of FH gene analysis in diagnosing homo-FH and confirmed extraordinarily high frequency of FH in the Hokuriku district of Japan.

Publication types

  • Evaluation Study

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Apolipoproteins B / genetics*
  • Asian People / genetics*
  • Child
  • Child, Preschool
  • DNA Mutational Analysis*
  • Female
  • Genetic Predisposition to Disease
  • Heterozygote
  • Homozygote
  • Humans
  • Hyperlipoproteinemia Type II / ethnology
  • Hyperlipoproteinemia Type II / genetics*
  • Incidence
  • Infant
  • Japan / epidemiology
  • Male
  • Middle Aged
  • Molecular Epidemiology
  • Mutation*
  • Phenotype
  • Polymerase Chain Reaction
  • Proprotein Convertase 9
  • Proprotein Convertases
  • Receptors, LDL / genetics*
  • Risk Assessment
  • Risk Factors
  • Serine Endopeptidases / genetics*
  • Young Adult


  • Apolipoproteins B
  • Receptors, LDL
  • PCSK9 protein, human
  • Proprotein Convertase 9
  • Proprotein Convertases
  • Serine Endopeptidases