Refereed journal article or data article (A1)
Genetic Factors Explain a Major Fraction of the 50% Lower Lipoprotein(a) Concentrations in Finns
List of Authors: Gertraud Erhart, Claudia Lamina, Terho Lehtimäki, Pedro Marques-Vidal, Mika Kähönen, Peter Vollenweider, Olli T. Raitakari, Gérard Waeber, Barbara Thorand, Konstantin Strauch, Christian Gieger, Thomas Meitinger, Annette Peters, Florian Kronenberg, Stefan Coassin
Publisher: LIPPINCOTT WILLIAMS & WILKINS
Publication year: 2018
Journal: Arteriosclerosis, Thrombosis, and Vascular Biology
Journal name in source: ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY
Journal acronym: ARTERIOSCL THROM VAS
Volume number: 38
Issue number: 5
Start page: 1230
End page: 1241
Number of pages: 12
ISSN: 1079-5642
eISSN: 1524-4636
DOI: http://dx.doi.org/10.1161/ATVBAHA.118.310865
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 >50000 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=10003). We observed approximate to 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.
