Question

However, lp (a) also contains a unique protein, apolipoprotein (a) [apo (a)], which is structurally different from other apolipoproteins, having a hydrophilic, carbohydrate-rich structure with no amphipathic helices

Answer 1

is structurally different from other apolipoproteins. The size of the apo(a) gene is highly variable, resulting in the protein
molecular weight ranging from 300 to 800 kDa; this large variation may be caused by neutral evolution in the absence
of any selection advantage. Apo(a) influences to a major extent metabolic and physicochemical properties of Lp(a), and
the size polymorphism of the apo(a) gene contributes to the pronounced heterogeneity of Lp(a). There is an inverse
relationship between apo(a) size and Lp(a) levels; however, this pattern is complex. For a given apo(a) size, there is a
considerable variation in Lp(a) levels across individuals, underscoring the importance to assess allele-specific Lp(a)
levels. Further, Lp(a) levels differ between populations, and blacks have generally higher levels than Asians and whites,
adjusting for apo(a) sizes. In addition to the apo(a) size polymorphism, an upstream pentanucleotide repeat (TTTTAn)
affects Lp(a) levels. Several meta-analyses have provided support for an association between Lp(a) and coronary artery
disease, and the levels of Lp(a) carried in particles with smaller size apo(a) isoforms are associated with cardiovascular
disease or with preclinical vascular changes. Further, there is an interaction between Lp(a) and other risk factors for
cardiovascular disease. The physiological role of Lp(a) is unknown, although a majority of studies implicate Lp(a) as
a risk factor. (Arterioscler Thromb Vasc Biol. 2004;24:2219-2226.)
Key Words: atherosclerosis genetics blacks lipids
Lipoprotein(a) [Lp(a)] was first described 40 years ago,
and interest in this entity is largely derived from its
putative role as a cardiovascular risk factor.1–3 Underlying
this concept is the realization that Lp(a) has many properties
in common with low-density lipoprotein (LDL), a well-
established atherogenic factor for coronary artery disease.2–5
Thus, the composition of the lipid moiety of Lp(a), including
its cholesteryl ester-rich core, is similar to that of LDL, and
the density distribution of the lipid moiety of Lp(a) in a given
subject closely mirrors that of LDL.6 Furthermore, like LDL,
each particle of Lp(a) has 1 molecule of apolipoprotein B-100
(apo B-100); both apolipoprotein B (apoB) and the lipid core
are pro-atherogenic.7 Also, Lp(a) clearance rates are similar
to those for LDL.8,9 However, Lp(a) contains a unique
protein, apolipoprotein(a) [apo(a)], which is structurally dif-
ferent from other apolipoproteins, having a hydrophilic,
carbohydrate-rich structure with no amphipathic helices.5,10,11
Apo(a) is linked to apoB through a single disulfide bond
connecting their C-terminal regions12–15 (Figure 1).
The presence of apo(a) influences to a major extent
metabolic and physicochemical properties of Lp(a).16 –18 No-
tably, the cysteine residue in apoB involved in the covalent
bond between apoB and apo(a) is close to the postulated LDL
receptor-binding region of apoB.19,20 It appears from many
clinical studies that Lp(a)