Prevalence and Clinical Correlates of Familial Hypercholesterolemia Founder Mutations in the General Population

Atherosclerosis. 2015 Jan;238(1):64-9. doi: 10.1016/j.atherosclerosis.2014.11.015. Epub 2014 Nov 18.


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.

Keywords: Familial hypercholesterolemia; Genetic epidemiology; Genetics; Low-density lipoprotein receptor; Mutation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Cohort Studies
  • Female
  • Finland / epidemiology
  • Founder Effect
  • Genotype
  • Geography
  • Heterozygote
  • Humans
  • Hypercholesterolemia / epidemiology*
  • Hypercholesterolemia / genetics*
  • Lipids / blood
  • Male
  • Middle Aged
  • Mutation*
  • Prevalence
  • Receptors, LDL / genetics*


  • LDLR protein, human
  • Lipids
  • Receptors, LDL