STRUCTURAL AND FUNCTIONAL POLYMORPHISM OF LIPOPROTEIN(A) - BIOLOGICALAND CLINICAL IMPLICATIONS

Lipoprotein(a) [Lp(a)], a variant of low-density lipoprotein, is heter ogeneous in density because of variability in the content and composit ion of its core lipids and size polymorphism of its specific glycoprot ein component, apolipoprotein(a) [apo(a)]. in some individuals, densit y polymorphism may also derive from the fact that Lp(a) contains 2 mol of apo(a) per mole of apoB100, contrary to the more common 1:1 molar stoichiometry. Moreover, the size of apo(a) is polymorphic because of variations in the number of kringle 4 type 2 repeats. Another type of apo(a) polymorphism is related to sequence mutations at the kringle le vel. Two mutations can occur in kringle 4 type 10: one, Trp(72) --> Ar g, is affiliated with an Lp(a) that is lysine-binding defective; the o ther, Met(66) --> Thr, with a normal lysine-binding function. Thus, Lp (a) is structurally and functionally polymorphic, a notion that must b e considered in assessing the cardiovascular pathogenicity of this lip oprotein variant and in immunoquantification assays.