Protein Z Levels, Protein Z G79A Polymorphism, and Prothrombotic Conditions

Abstract

To the Editor: We read with great interest the article on protein Z gene polymorphisms, protein Z concentrations, and ischemic stroke published by Staton et al.1 The authors examine protein Z concentrations and 2 common polymorphisms of the protein Z gene in patients with a first-ever ischemic stroke and conclude that high levels of protein Z are prothrombotic and that the 79AA genotype of the G79A polymorphism is protective for the ischemic stroke. The conclusions drawn by Staton et al seem questionable because of several flaws. First, the hypothesis that high levels of protein Z are prothrombotic is, to date, not supported by the pathophysiology, because the role of protein Z has been demonstrated to be the inhibition of activated factor X through the formation of a complex with protein Z–dependent protease inhibitor. Consequently, low levels of protein Z are expected to be prothrombotic. In line with this theory, the majority of the studies in this field have reported low levels of protein Z in association with prothrombotic conditions. Actually, only 2 studies have reported that …