Development of a genotype-dependent therapeutic strategy for preventing venous thromboembolism

2023 Fiscal Year Final Research Report

• Project/Area Number: 18K07486
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 52010:General internal medicine-related
• Research Institution: Nakamura Gakuen College
• Principal Investigator: Tsuda Hiroko 中村学園大学, 流通科学研究所, 客員研究員 (30180003)
• Co-Investigator(Kenkyū-buntansha): 能口 健太 中村学園大学, 栄養科学部, 助教 (90757494) ; 宮 真南 中村学園大学, 栄養科学部, 助手 (30828182)
• Project Period (FY): 2018-04-01 – 2024-03-31
• Keywords: 遺伝性血栓性素因 / プロテインS / 若年日本人女性 / 予防治療戦略 / 食因子

Outline of Final Research Achievements

A protein S gene polymorphism with decreased activity, Protein S Tokushima, is a genetic risk factor for venous thromboembolism prevalent among the Japanese population, with an incidence of 2%. We found the plasma levels of total protein S activity and antigen of Japanese female university students, who were homozygous for the wild allele of Protein S Tokushima, were positively correlated with the levels of apolipoprotein C-Ⅱ, LDL cholesterol, and HbA1c during fasting. However, these levels did not change after consuming high-fat or high-carbohydrate meals. No food group correlated with total protein S activity and antigen levels. The expression of the protein S gene in HepG2 cells decreased when the glucose concentration in the medium was lowered. It is suggested that protein S activity is not affected by food intake and is positively correlated with fasting plasma glucose levels.

Free Research Field

血栓止血学

Academic Significance and Societal Importance of the Research Achievements

Protein S TokushimaはプロテインSの抗凝固活性低下をきたす遺伝子多型で静脈血栓塞栓症の遺伝素因である。我が国には約200万人の変異保有者が存在するが、白人、中国人、韓国人、東南アジア人、ブラジル人では同定されていない。静脈血栓塞栓症の予防・治療法は主に白人を対象として研究されており、食生活に着目したものはない。したがって、日本人固有の遺伝性血栓性素因を考慮し、食因子に焦点をあてた本研究の研究成果は、今後の日本における静脈血栓塞栓症の予防・治療の充実に大きく貢献するものと確信する。