Lipoprotein(a) [Lp(a)], an independent risk factor for the development of
atherosclerosis, contains an
apolipoprotein(a) [
apo(a)] moiety covalently linked to a
LDL moiety.
Apo(a) is a
glycoprotein homologous to
plasminogen as it contains multiple repeats of a
lysine binding domain resembling
plasminogen kringle IV (K.IV). The multiple K.IV repeats can be differentiated in ten types that show a variation in their
lysine binding capacity. Since K.IV type 10 shows the highest conservation of the
amino acids postulated to form the
lysine binding pocket, this kringle is suggested to be the main
lysine binding site of
apo(a). Recently, a T-->C polymorphism in the
apo(a)-gene was reported, leading to a Met-->Thr substitution at
amino acid position 66 of K.IV type 10, in the vicinity of the postulated
lysine binding pocket. To investigate the significance of this substitution on some in vitro characteristics of Lp(a), the affinity for
lysine-Sepharose and the binding affinity for limited
plasmin digested des AA
fibrin (Desafib-X) of the two subtypes was determined using plasma of donors homozygous for the polymorphism. These studies revealed a large heterogeneity in the binding characteristics, irrespective of the subtype. The comparison of the allele frequencies of this polymorphism in 155 patients having symptomatic
atherosclerosis versus 153 normolipidemic controls revealed no significant differences. In conclusion, this study suggests that the presence of either a Met66 or a Thr66 residue in K.IV type 10 of
apo(a) has no consequences for the binding characteristics of Lp(a) toward
lysine-Sepharose or Desafib-X, nor is it associated with the presence of symptomatic
atherosclerosis.