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Arterioscler Thromb Vasc Biol. 2018 May;38(5):1230-1241. doi: 10.1161/ATVBAHA.118.310865. Epub 2018 Mar 22.

Genetic Factors Explain a Major Fraction of the 50% Lower Lipoprotein(a) Concentrations in Finns.

Author information

1
From the Division of Genetic Epidemiology, Department of Medical Genetics, Molecular and Clinical Pharmacology, Medical University of Innsbruck, Austria (G.E., C.L., F.K., S.C.).
2
Department of Clinical Chemistry, Fimlab Laboratories (T.L.).
3
Finnish Cardiovascular Research Center (T.L., M.K.).
4
Department of Medicine, Internal Medicine, Lausanne University Hospital, Switzerland (P.M.-V., P.V., G.W.).
5
Department of Clinical Physiology, Tampere University Hospital (M.K.), University of Tampere, Finland.
6
Department of Clinical Physiology and Nuclear Medicine, Turku University Hospital, Finland (O.T.R.).
7
Research Centre of Applied and Preventive Cardiovascular Medicine, University of Turku, Finland (O.T.R.).
8
Institute of Epidemiology II (B.T., C.G., A.P.).
9
German Center for Diabetes Research, Neuherberg, Germany (B.T., A.P.).
10
Institute of Genetic Epidemiology (K.S., C.G.).
11
Institute of Medical Informatics, Biometry, and Epidemiology, Ludwig-Maximilians-Universität, Munich, Germany (K.S.).
12
Research Unit of Molecular Epidemiology (C.G.), Helmholtz Zentrum München-German Research Center for Environmental Health, Neuherberg, Germany.
13
Institute of Human Genetics, Technische Universität München, Germany (T.M.).
14
Institute of Human Genetics, Helmholtz Zentrum München, Neuherberg, Germany (T.M.).
15
Munich Cluster for Systems Neurology, Germany (T.M.).
16
German Centre for Cardiovascular Research, Partner Site Munich Heart Alliance (A.P.).
17
From the Division of Genetic Epidemiology, Department of Medical Genetics, Molecular and Clinical Pharmacology, Medical University of Innsbruck, Austria (G.E., C.L., F.K., S.C.) stefan.coassin@i-med.ac.at.

Abstract

OBJECTIVE:

Lp(a) (lipoprotein(a)) concentrations are widely genetically determined by the LPA isoforms and show 5-fold interpopulation differences. Two- to 3-fold differences have been reported even within Europe. Finns represent a distinctive population isolate within Europe and have been repeatedly reported to present lower Lp(a) concentrations than Central Europeans. The significance of this finding was unclear for a long time because of the difficult comparability of Lp(a) assays. Recently, a large standardized study in >50 000 individuals from 7 European populations confirmed this observation but could not provide insights into the causes.

APPROACH AND RESULTS:

We investigated Lp(a) concentrations, LPA isoforms, and genotypes of established genetic variants affecting Lp(a) concentrations (LPA variants, APOE isoforms, and PCSK9 R46L) in the Finnish YFS (Cardiovascular Risk in Young Finns Study) population (n=2281) and 3 Non-Finnish Central European populations (n=10 003). We observed ≈50% lower Lp(a) concentrations in Finns. The isoform distribution was shifted toward longer isoforms, and the percentage of low-molecular-weight isoform carriers was reduced. Most interestingly, however, Lp(a) was reduced in each single-isoform group. In contrast to the known inverse relationship between LPA isoforms and Lp(a) concentrations, especially very short isoforms presented unexpectedly low Lp(a) concentrations in Finns. The investigated genetic variants, as well as age, sex, and renal function, explained 71.8% of the observed population differences.

CONCLUSIONS:

The population differences in Lp(a) concentrations between Finnish and Central European populations originate not only from a different LPA isoform distribution but suggest the existence of novel functional variation in the small-isoform range.

KEYWORDS:

atherosclerosis; genetics, population; lipoprotein(a); risk factors

PMID:
29567679
PMCID:
PMC5943067
DOI:
10.1161/ATVBAHA.118.310865
[Indexed for MEDLINE]
Free PMC Article

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