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

Area of Science:

• Genetics and Molecular Biology
• Thrombophilia and Hemostasis Research
• Population Health Studies

Background:

• Disease-associated mutations exhibit varying frequencies across ethnic groups, underscoring the need for ethnicity-specific investigations.
• Previous studies have indicated ethnic disparities in the genetic underpinnings of thrombophilia.

Purpose of the Study:

• To investigate the prevalence of deficiencies in plasma proteins C, S, antithrombin, and plasminogen within the Japanese population.
• To identify genetic factors contributing to deep vein thrombosis (DVT) in this demographic.
• To assess the clinical significance of the protein S K196E mutation in the Japanese population.

Main Methods:

• Conducted a large-scale analysis of plasma activities for proteins C, S, antithrombin, and plasminogen in the general Japanese population.
• Evaluated the genetic contribution of specific mutations, including protein S K196E, to the risk of deep vein thrombosis.
• Estimated allele frequencies and calculated the potential number of affected individuals.

Main Results:

• Prevalence of deficiencies: Protein C (0.13%), antithrombin (0.15%), protein S (1.12%), and plasminogen (4.29%).
• Identified protein S mutation K196E as a significant genetic risk factor for DVT in the Japanese population, with an estimated allele frequency of 0.009.
• Approximately 1 in 12,000 Japanese individuals may be homozygous for the K196E allele, potentially affecting up to 10,000 people.

Conclusions:

• A substantial portion of the Japanese population carries the protein S E allele, increasing their risk for deep vein thrombosis.
• The high frequency and strong association of the protein S K196E mutation with DVT suggest the value of large-scale screening.
• Individuals identified with this allele should be advised to mitigate environmental risk factors associated with DVT.