© 1997 American Heart Association, Inc.
Articles |
Familial Hypercholesterolemia in the Finnish North Karelia
A Molecular, Clinical, and Genealogical Study
From the Departments of Medicine (A.F.V., K.K.) and History (K-M.P.), University of Helsinki, Helsinki, Finland; the Central Hospital of North Karelia (H.T.), Joensuu, Finland; the North Karelian Data Base (P.R.), Joensuu, Finland, and the Department of Endocrinology (T.K.), University of Lund, Malmö, Sweden.
Correspondence to Kimmo Kontula, MD, Professor of Molecular Medicine, Department of Medicine, University of Helsinki, Haartmaninkatu 4, FIN-00290 Helsinki Finland.
Abstract A specific mutation termed FH-North Karelia
[FH-NK] accounts for almost 90% of familial
hypercholesterolemia [FH] cases in the
Finnish North Karelia, with a population of about 180 000. Extensive
search for its presence in the entire North Karelia province revealed
340 carriers of this mutation. Other mutations of the LDL receptor
[LDLR] gene accounted for 67 cases of heterozygous FH. This gives a
minimum FH prevalence of 1 in 441 inhabitants in North Karelia, with
the highest density of patients in the Polvijärvi commune (1 in
143 inhabitants). Old parish records, confirmation records, and
tax records were used to track a common ancestor for most of the
present-day North Karelian FH-NK patients in the village of Puso,
located within an area where the FH prevalence today is the highest.
DNA analysis indicated that 2% of the subjects aged 1 to
25 years would have been diagnosed as false-negative and 7% as
false-positive FH patients on the basis of LDL cholesterol
[LDL-C] determinations alone. Common genetic variations of
apolipoprotein E [apoE], XbaI, polymorphism of
apolipoprotein B [apoB], and PvuII polymorphism of
the intact LDLR allele contributed little to serum lipid variation
in established carriers of the FH-NK allele, although apoE2/4
genotype and the presence of the PvuII
restriction site tended to be associated with relatively low LDL-C
levels. Coronary heart disease (CHD) was present in 65
(30%) out of the 179 FH gene carriers aged 
25 years, and 19
individuals had a previous history of acute myocardial infarction
(AMI). The average age (mean±SD) at onset of CHD was 42±7 years for
males and 48±11 years for females (P<.05). In stepwise
logistic regression analysis carried out in carriers of the
FH-NK allele, age, gender, smoking, and apoE allele E2 all
emerged as independent determinants of risk of CHD or AMI. It may be
concluded that the relatively high prevalence of FH patients in North
Karelia province provides a unique founder population in which genetic
and nongenetic factors modifying the course of FH can be effectively
investigated.
Key Words: LDL receptor • diagnosis • phenotype • genealogy
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