Genetic risk factors for deep vein thrombosis among Japanese: importance of protein S K196E mutation.

There is mounting evidence that mutations associated with a given disease arise with different frequencies among ethnic groups, thus ethnicity-specific studies are needed to identify causative mutations and properly assess risk. In particular, ethnic differences in the genetic background of thrombophilia have been reported. We recently conducted a large-scale analysis of the plasma activities of proteins C, S, antithrombin, and plasminogen within the Japanese general population. We found age- and sex-related differences and estimated the prevalence of deficiencies of protein C (0.13%), antithrombin (0.15%), protein S (1.12%), and plasminogen (4.29%). We also evaluated the genetic contribution to deep vein thrombosis and found that protein S mutation K196E is a genetic risk factor in the Japanese population. We estimated allele frequency to be 0.009, suggesting that 1 of 12,000 Japanese may be homozygous for the E allele, thus possibly as many as 10,000 individuals. Accordingly, a substantial proportion of the Japanese population carries the protein S E allele and is at risk of developing deep vein thrombosis. Given the frequency of this mutation and its strong correlation with deep vein thrombosis, it may be valuable to conduct a large-scale screening for this allele and advise concerned persons to avoid environmental risk factors known to be associated with deep vein thrombosis.