Protein Z-dependent protease inhibitor W303X mutation in venous thrombosis.

In reply to the study by Gonzalez-Conjero et al, we found their results on 218 Spanish White patients very interesting. As suggested in their article, there does indeed appear to be an ethnic bias and possible founder affect with regard to the W303X mutation in thrombosis patients. The frequency of both the Factor V Leiden mutation and the prothrombin 20210A variant also varies within White populations. The allelic frequencies for the factor V Leiden mutation in White subpopulations ranges from <1% to 8.5% (Zivelin et al, 1997) and appears to be absent or in very low frequencies in nonEuropean White people and totally absent in other ethnic groups (Rees et al, 1995). The 250 patients and 250 control subjects used in our study (Van de Water et al, 2004) were European White people of whom >90% were of northern European origin (McKinnon et al, 1997) with a strong influence from UK immigration. In our study we also identified another stop codon mutation (R67X) in three of our thrombosis patient cohort (n 1⁄4 250). It is unfortunate that Gonzalez-Conjero et al. did not extend their study to include the R67X mutation within the ZPI gene as well. Further studies of ZPI mutations in thrombosis patient populations are required, especially those in patients of northern European background, to evaluate the role of protein Z-dependent protease inhibitor in haemostasis and thrombosis. Paul Harper