A single point mutation (Trp72-->Arg) in human apo(a) kringle 4-37 associated with a lysine binding defect in Lp(a).

Human lipoprotein(a) or Lp(a) binds, like plasminogen, to lysine Sepharose. However, contrary to plasminogen in which kringles 1 and 4 have been implicated, the binding site or sites on apo(a), the specific glycoprotein of Lp(a), have not been determined. For the first time we now report the occurrence of a human Lp(a) that has a mutant form of apo(a) where Arg has replaced Trp in position 72 of kringle 4-37 and is unable to bind to lysine Sepharose. This observation suggests that Trp72 of apo(a) kringle 4-37 may play a dominant role in lysine binding. Lysine binding has been associated with the thrombogenic potential of Lp(a). Thus, the Trp72-->Arg mutation may render Lp(a) 'benign' from the cardiovascular viewpoint.