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Lipoprotein(a): resurrected by genetics
Author(s) -
Kronenberg F.,
Utermann G.
Publication year - 2013
Publication title -
journal of internal medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.625
H-Index - 160
eISSN - 1365-2796
pISSN - 0954-6820
DOI - 10.1111/j.1365-2796.2012.02592.x
Subject(s) - genetics , allele , mendelian randomization , population , lipoprotein(a) , lipoprotein , locus (genetics) , medicine , biology , gene , cholesterol , genotype , genetic variants , environmental health
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.