title: Molecular genetic epidemiology of homozygous familial hypercholesterolemia in the Hokuriku district of Japan.
abstract: OBJECTIVE
  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.
authors.affiliation: Department of Lipidology, Graduate School of Medical Science, Kanazawa University, Kanazawa, Japan. mabuchi@med.kanazawa-u.ac.jp
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Mabuchi
authors.forename: Atsushi
authors.initials: A
authors.lastname: Nohara
authors.forename: Tohru
authors.initials: T
authors.lastname: Noguchi
authors.forename: Junji
authors.initials: J
authors.lastname: Kobayashi
authors.forename: Masa-Aki
authors.initials: MA
authors.lastname: Kawashiri
authors.forename: Hayato
authors.initials: H
authors.lastname: Tada
authors.forename: Chiaki
authors.initials: C
authors.lastname: Nakanishi
authors.forename: Mika
authors.initials: M
authors.lastname: Mori
authors.forename: Masakazu
authors.initials: M
authors.lastname: Yamagishi
authors.forename: Akihiro
authors.initials: A
authors.lastname: Inazu
authors.forename: Junji
authors.initials: J
authors.lastname: Koizumi
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001055:Apolipoproteins B / Q000235:genetics*; D044466:Asian People / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D004252:DNA Mutational Analysis; D005260:Female; D020022:Genetic Predisposition to Disease; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D006938:Hyperlipoproteinemia Type II / Q000208:ethnology / Q000235:genetics*; D015994:Incidence; D007223:Infant; D007564:Japan / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D017720:Molecular Epidemiology; D009154:Mutation; D010641:Phenotype; D016133:Polymerase Chain Reaction; D000071449:Proprotein Convertase 9; D043484:Proprotein Convertases; D011973:Receptors, LDL / Q000235:genetics*; D018570:Risk Assessment; D012307:Risk Factors; D012697:Serine Endopeptidases / Q000235:genetics*; D055815:Young Adult
chemical_list: D001055:Apolipoproteins B; D011973:Receptors, LDL; C472125:PCSK9 protein, human; D000071449:Proprotein Convertase 9; D043484:Proprotein Convertases; D012697:Serine Endopeptidases