title: Prevalence and clinical correlates of familial hypercholesterolemia founder mutations in the general population.
abstract: OBJECTIVE
  This study aimed to investigate the exact prevalence of familial hypercholesterolemia (FH) in the general population, taking advantage of the fact that five low-density lipoprotein receptor (LDLR) founder mutations account for 78% of FH cases in Finland.
  
  
  METHODS
  Five LDLR founder mutations, FH-North Karelia, FH-Helsinki, FH-Pogosta, FH-Turku, and FH-Pori, were genotyped and serum lipid levels were measured in a large collection of Finnish population cohorts (n = 28,465), including the National FINRISK Study and the Health 2000 Study. Follow-up data were obtained from national healthcare registries.
  
  
  RESULTS
  The combined prevalence of three of the five FH founder mutations (FH-North Karelia, FH-Helsinki, and FH-Pogosta) was 0.12% (95% CI 0.07-0.16%), while FH-Turku and FH-Pori were not identified in the present sample cohort. Our data suggest that the estimated total prevalence of FH in Finland is at least 0.17%. Approximately half of the 35 FH mutation carriers used lipid-lowering medication at the time of the baseline investigation. LDL cholesterol levels were on average 2 mmol/L higher in mutation carriers than in non-carriers (p < 0.001) but did not differ between FH mutation carriers with and without lipid-lowering medication. During the follow-up for 13 years, one mutation carrier encountered a probable sudden cardiac death, two mutation carriers suffered from a stroke, and one from a myocardial infarction.
  
  
  CONCLUSIONS
  In Finland, at least 1 in 600 individuals is estimated to have FH. A marked undertreatment of FH was observed in LDLR mutation carriers.
authors.affiliation: Department of Medicine, University of Helsinki and Helsinki University Central Hospital, Helsinki, Finland.
authors.forename: Annukka M
authors.initials: AM
authors.lastname: Lahtinen
authors.affiliation: National Institute for Health and Welfare, Helsinki and Turku, Finland.
authors.forename: Aki S
authors.initials: AS
authors.lastname: Havulinna
authors.affiliation: National Institute for Health and Welfare, Helsinki and Turku, Finland.
authors.forename: Antti
authors.initials: A
authors.lastname: Jula
authors.affiliation: National Institute for Health and Welfare, Helsinki and Turku, Finland.
authors.forename: Veikko
authors.initials: V
authors.lastname: Salomaa
authors.affiliation: Department of Medicine, University of Helsinki and Helsinki University Central Hospital, Helsinki, Finland. Electronic address: kimmo.kontula@hus.fi.
authors.forename: Kimmo
authors.initials: K
authors.lastname: Kontula
mesh_terms: D000328:Adult; D000368:Aged; D015331:Cohort Studies; D005260:Female; D005387:Finland / Q000453:epidemiology; D018703:Founder Effect; D005838:Genotype; D005843:Geography; D006579:Heterozygote; D006801:Humans; D006937:Hypercholesterolemia / Q000453:epidemiology* / Q000235:genetics*; D008055:Lipids / Q000097:blood; D008297:Male; D008875:Middle Aged; D009154:Mutation; D015995:Prevalence; D011973:Receptors, LDL / Q000235:genetics*
chemical_list: C573412:LDLR protein, human; D008055:Lipids; D011973:Receptors, LDL
keywords: Familial hypercholesterolemia; Genetic epidemiology; Genetics; Low-density lipoprotein receptor; Mutation