The mysteries of lipoprotein(a) and cardiovascular disease revisited.

t m r h h p g e e 3 t L g a a b m i t s a p i g c f o fi l f b a w i v c p t b p he discovery of lipoprotein(a) (Lp[a]) traces back to the 960s, with fundamental insights into particle structure and eritability gained in the 1970s (1,2). Lipoprotein(a) is omposed of a low-density lipoprotein (LDL) moiety and he covalently linked carbohydrate-rich apolipoprotein(a) apo[a]), which is responsible for the unique properties of he particle. Lipoprotein(a) is a recent evolutionary arrival pecific to humans and nonhuman primates, with the apo(a) omponent having originated from a duplication of the lasminogen gene. Like plasminogen, apo(a) is characterzed by loop structures called kringles. It contains an inactive rotease domain, 1 kringle V and 10 different types of ringle IV motifs, with the kringle IV type 2 (KIV2) ccurring in multiple copies (3 to 50) regulated by a opy-number variation in the apo(a) gene. The heterogenety in the number of KIV2 copies accounts for approximately ne-half of the substantial (up to 1,000-fold) interindividual ariability of Lp(a) plasma levels. Recent large-scale surveys nraveled a complex genetic architecture of Lp(a) beyond he classic copy-number variation (3,4). Multiple (lowrevalence) single-nucleotide polymorphisms in the Lp(a) ocus on chromosome 6q were reported to partly explain the ide range of Lp(a) levels in carriers of the same apo(a) soform and discrepancy in Lp(a) levels between people of frican descent and whites.