Identification of mutations in human apolipoprotein(a) kringle 4-37 from the study of the DNA of peripheral blood lymphocytes: relevance to the role of lipoprotein(a) in atherothrombosis.

Using a technique that amplifies the DNA region coding for kringle 4-37 of human apolipoprotein(a) we have identified 2 mutations, trp72-->arg and met66-->thr. The former was only present in 2 of the 100 subjects studied, was associated with a lysine-binding defective lipoprotein(a) [Lp(a)], low plasma levels of Lp(a), and no evidence of atherosclerotic cardiovascular disease (ASCVD). The other mutation was present in about 40% of the subjects who had either normal or high plasma levels of Lp(a) and a personal and/or familial history of ASCVD. These studies show that human kringle 4-37 is mutable and that mutations in this kringle can affect the lysine-binding properties of apo(a) and, perhaps, the atherothrombogenic potential of Lp(a).