Plasma protein S activity correlates with protein S genotype but is not sensitive to identify K196E mutant carriers

Protein S (PS) is an anticoagulant protein that functions as a cofactor for activated protein C (APC), and congenital PS deficiency is a well-known risk factor for the development of deep vein thrombosis (DVT). Recently, we and others identified the K196E missense mutation in the second epidermal growth factor-like domain of PS as a genetic risk factor for DVT in the Japanese population. The incidence of this mutation is high in the Japanese population.

In the present study, we investigated the relationship between plasma PS activity and the presence of the K196E mutation.

We measured PS activity as a cofactor activity for APC in 1,862 Japanese individuals and determined the PS K196E genotype in this population.

Individuals heterozygous for the mutant E-allele had lower plasma PS activity than wildtype subjects (mean +/- SD, 71.9 +/- 17.6%, n = 34 vs. 87.9 +/- 19.8%, n = 1,828, P < 0.0001). However, the PS activity of several heterozygous individuals (n = 8) was greater than the population average. In contrast, multiple wildtype subjects (n = 26) had PS activity less than 2 SD below the population mean, indicating that other genetic or environmental factors affect PS activity.

Plasma PS activity itself is not suitable for identifying PS 196E carriers and other methods are required for carrier detection.