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

Overview

Journal Arterioscler Thromb Vasc Biol

Date 2018 Mar 24

PMID 29567679

Citations 16

Authors

Gertraud Erhart

Claudia Lamina

Terho Lehtimaki

Pedro Marques-Vidal

Mika Kahonen

Peter Vollenweider

Olli T Raitakari

Gerard Waeber

Barbara Thorand

Konstantin Strauch

Christian Gieger

Thomas Meitinger

Annette Peters

Florian Kronenberg

Stefan Coassin

Affiliations

Soon will be listed here.

Abstract

Objective: Lp(a) (lipoprotein(a)) concentrations are widely genetically determined by the 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, isoforms, and genotypes of established genetic variants affecting Lp(a) concentrations ( variants, isoforms, and 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 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 isoform distribution but suggest the existence of novel functional variation in the small-isoform range.

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