Key result
Lipoprotein(a) plasma concentrations are highly heritable, with over 50% of variation attributable to genetic variation in the LPA gene locus, particularly the KIV-2 copy number variant.
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Lipoprotein(a) is a highly heritable cardiovascular risk factor whose plasma concentrations are largely determined by genetic variation in the LPA gene locus.
Lipoprotein(a) [Lp(a)], first described in 1963 by the Norwegian Kaare Berg, consists of a low density lipoprotein (LDL)-like particle with an additional apolipoprotein covalently bound to apolipoprotein B; apolipoprotein(a) [apo(a)] (1). Lp(a) plasma concentrations are highly heritable with >50% of the variation in levels attributable to genetic variation in the LPA gene locus coding for apo(a) synthesized by hepatocytes. Of particular importance is the so-called kringle-IV type 2 (KIV-2) LPA copy number variant (CNV) determining the number of kringle-shaped protein structures in apo(a), thus determining apo(a) isoform size, which correlates inversely with plasma Lp(a) levels (1).
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Pia R. Kamstrup (2017) conducted a review in cardiovascular disease. Lipoprotein(a) was evaluated. Lipoprotein(a) plasma concentrations are highly heritable, with over 50% of variation attributable to genetic variation in the LPA gene locus, particularly the KIV-2 copy number variant.
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