Familial hypercholesterolaemia in Finland: common, rare and mild mutationsof the LDL receptor and their clinical consequences

Familial hypercholesterolaemia (FH) is an autosomal co-dominantly inherited condition resulting from mutations of the low-density lipoprotein (LDL) re ceptor which occur in heterozygous form in approximately one in 500 individ uals. Clinically, FH is characterized by 2-3-fold elevation of serum LDL ch olesterol levels, accelerated development of atherosclerotic vascular disea se, and, if untreated, shortened lifespan. The Finnish population, which re presents a genetic isolate, offers exceptional possibilities for genetic-ep idemiological studies on FH, as a handful of founder gene mutations account for the majority of FH cases in Finland. This review summarizes data from our FH studies carried out since 1985. We wish to emphasize the continuum o f genotype-phenotype relationships, the importance of molecular diagnosis, the detection of novel risk factors of vascular disease, and innovations in hibiting cholesterol absorption for the modern treatment of FH.