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Plasma protein S activity correlates with protein S genotype but is not sensitive to identify K196E mutant carriers
Author(s) -
KIMURA R.,
SAKATA T.,
KOKUBO Y.,
OKAMOTO A.,
OKAYAMA A.,
TOMOIKE H.,
MIYATA T.
Publication year - 2006
Publication title -
journal of thrombosis and haemostasis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.947
H-Index - 178
eISSN - 1538-7836
pISSN - 1538-7933
DOI - 10.1111/j.1538-7836.2006.02071.x
Subject(s) - protein c , missense mutation , population , genotype , mutant , allele , mutation , wild type , mutant protein , factor v , protein s , heterozygote advantage , medicine , endocrinology , biology , microbiology and biotechnology , genetics , thrombosis , gene , environmental health
Summary. Background: 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. Objectives: In the present study, we investigated the relationship between plasma PS activity and the presence of the K196E mutation. Patients and methods: We measured PS activity as a cofactor activity for APC in 1862 Japanese individuals and determined the PS K196E genotype in this population. Results: 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 = 1828, 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. Conclusions: Plasma PS activity itself is not suitable for identifying PS 196E carriers and other methods are required for carrier detection.