Cited by 521Lipoproteins and Cardiovascular HealthGenetic Associations and EpidemiologyAtherosclerosis and Cardiovascular Diseases

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Lipoprotein(a): resurrected by genetics

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Kronenberg, F., Utermann, G.·2013·Journal of Internal Medicine

DOI 10.1111/j.1365-2796.2012.02592.x

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Abstract

Plasma lipoprotein(a) [L p(a)] is a quantitative genetic trait with a very broad and skewed distribution, which is largely controlled by genetic variants at the LPA locus on chromosome 6q27. Based on genetic evidence provided by studies conducted over the last two decades, L p(a) is currently considered to be the strongest genetic risk factor for coronary heart disease (CHD). The copy number variation of kringle IV in the LPA gene has been strongly associated with both L p(a) levels in plasma and risk of CHD, thereby fulfilling the main criterion for causality in a M endelian randomization approach. Alleles with a low kringle IV copy number that together have a population frequency of 25–35% are associated with a doubling of the relative risk for outcomes, which is exceptional in the field of complex genetic phenotypes. The recently identified binding of oxidized phospholipids to L p(a) is considered as one of the possible mechanisms that may explain the pathogenicity of L p(a). Drugs that have been shown to lower L p(a) have pleiotropic effects on other CHD risk factors, and an improvement of cardiovascular endpoints is up to now lacking. However, it has been established in a proof of principle study that lowering of very high L p(a) by apheresis in high‐risk patients with already maximally reduced low‐density lipoprotein cholesterol levels can dramatically reduce major coronary events.

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Authors: Kronenberg, F., & Utermann, G.
Affiliations: Innsbruck Medical University (AT)
Corresponding author: Utermann, G.
ORCID: Kronenberg, F.
Venue: Journal of Internal Medicine
Publisher: Wiley
Published: 2012-11-12
Volume: 273
Issue: 1
Pages: 6-30
ISSN: 0954-6820 (ISSN-L)
1365-2796
DOI: 10.1111/j.1365-2796.2012.02592.x
OpenAlex: W1988877980
Cited by: 521
References: 203
Citations by year: 2026: 40 · 2025: 38 · 2024: 39 · 2023: 41 · 2022: 45 · 2021: 42 · 2020: 36 · 2019: 48 · 2018: 35 · 2017: 36 · 2016: 42 · 2015: 38 · 2014: 20 · 2013: 17 · 2012: 2
FWCI: 4.75
Type: journal article
Language: en
Open access: bronze
doi.org
Licence: onlinelibrary.wiley.com/termsAndConditions#vor (vor)
Locations: Journal of Internal Medicine (publishedVersion)
PubMed (publishedVersion)
Funders: Austrian Science Fund
Oesterreichische Nationalbank
Standortagentur Tirol
Topics: Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Lipoproteins and Cardiovascular Health
Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
Life Sciences › Immunology and Microbiology › Immunology › Atherosclerosis and Cardiovascular Diseases
Keywords: lipoprotein(a), LPA gene, coronary heart disease risk, genetic risk factors, Mendelian randomization, apheresis, cardiovascular risk reduction
MeSH terms: Alleles, Coronary Artery Disease, DNA, Gene Frequency, Humans, Polymorphism, Genetic, Lipoprotein(a), Genetic Predisposition to Disease, Mendelian Randomization Analysis

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