한국인 임산부에서 단백질 C와 단백질 S 활성도 변화 및 임신 합병증과의 연관성 조사
Changes in Protein C and Protein S Activities and the Association with Adverse Pregnancy Outcomes in Pregnant Korean Women
2
조회
0
다운로드
0
인용
0
참고문헌
키워드
초록
배경: 임신 중 응고인자의 변화는 인종에 따라 차이가 있으나 한국인을 대상으로 한 연구는 부족하다. 따라서 한국인에서 임신 각분기별 및 산후 기간의 단백질 C와 단백질 S의 활성도 변화를 측정하고 비임신 대조군과 그 값을 비교한 후, 임신 합병증과의 연관성을 분석하였다. 방법: 단백질 C와 단백질 S의 활성도는 chromogenic analysis로측정하였다. 비임신과 임신 각 분기별 단백질 활성도의 비교는Kruskal-Wallis test를 사용하였고 임신 합병증과 단백질 활성도의연관성은 Mann-Whitney U-test를 사용하였고 단백질 활성도의 변화가 임신 합병증에 미치는 영향은 linear logistic regression 분석을 통해 알아보았다. 결과: 단백질 C 활성도는 비임신보다 임신 시 상승하였고 단백질 S 활성도는 반대로 임신 시 감소했다. 하지만 임신 기간 중 서양인에서는 단백질 S 활성도가 분기별 단계적 감소를 보이는 반면 한국여성에서는 임신 1삼분기에 급격히 감소한 이후 임신 기간 동안 정체를 보였다. 또한 3삼분기의 단백질 활성도가 기준 값에서 벗어난경우 태아성장제한 및 임신성 고혈압과 임신성 당뇨 발생이 증가하였다. 결론: 한국인의 임신 중 단백질 C와 단백질 S의 활성도는 서양인과 차이가 있었고 임신 3삼분기 단백질 S 활성도의 감소는 임신성고혈압 발생과 유의한 연관이 있었다. 이는 한국인 임산부에 적합한 응고인자 활성도의 참조 구간을 설정하고 임신 합병증 예측에활용하기 위해 추가 연구가 필요함을 시사한다.
Abstract
Background: We analyzed the changes in protein C and protein S activities in each trimester and postpartum period in pregnant Korean women and their association with adverse pregnancy outcomes. Methods: This prospective study included 172 singleton pregnant women and 53 non-pregnant women. Protein C and protein S activities were measured using chromogenic analysis, and differences between each group and the relationship of the protein activities with adverse pregnancy outcomes were analyzed. Results: Protein C activity was significantly increased in the second and third trimesters and in the postpartum period (P <0.001, P =0.017, and P <0.001, respectively), whereas protein S activity was significantly decreased throughout pregnancy compared to that in the non-pregnant group (P <0.001, P <0.001, P <0.001, and P =0.011, respectively). In the third trimester of pregnancy, protein C activity was significantly higher in women who delivered babies with fetal growth restriction (40.1% vs. 27.6%, P =0.040). Protein S activity was significantly lower in pregnant women who developed pregnancy-induced hypertension/preeclampsia and gestational diabetes than in women who did not develop these complications (10.1% vs. 35.0%, P =0.008; and 25.9% vs. 38.8%, P =0.042, respectively). Conclusions: Protein C activity tended to increase during pregnancy and the postpartum period compared to that in the non-pregnant period. Protein S activity decreased rapidly from the first trimester and continued decreasing during pregnancy and the postpartum period. Reduced protein S activity in the third trimester is associated with pregnancy-induced hypertension and preeclampsia.
참고문헌 (30)
- James AH, "Pregnancy-associated thrombosis", Hematology Am Soc Hematol Educ Program, 2009, pp.277~285 (2009)
- Kujovich JL, "Hormones and pregnancy : thromboembolic risks for women", Br J Haematol, 126, pp.443~454 (2004)
- Franchini M, "Haemostasis and pregnancy", Thromb Haemost, 95, pp.401~413 (2006)
- Simmonds RE, "Identification of 19 protein S gene mutations in patients with phenotypic protein S deficiency and thrombosis. Protein S Study Group", Blood, 88, pp.4195~4204 (1996)
- Uchikova EH, "Changes in haemostasis during normal pregnancy", Eur J Obstet Gynecol Reprod Biol, 119, pp.185~188 (2005)
- Hamasaki N, "Recent advances in thrombosis and hemostasis 2008", pp.597~613 (2008), Springer
- Alfirevic Z, "How strong is the association between maternal thrombophilia and adverse pregnancy outcome? : a systematic review", Eur J Obstet Gynecol Reprod Biol, 101, pp.6~14 (2002)
- Okoye HC, "Associations between pre-eclampsia and protein C and protein S levels among pregnant Nigerian women", Int J Gynaecol Obstet, 137, pp.26~30 (2017)
- Ebina Y, "Low levels of plasma protein S, protein C and coagulation factor XII during early pregnancy and adverse pregnancy outcome", Thromb Haemost, 114, pp.65~69 (2015)
- Hojo S, "Decreased maternal protein S activity is associated with fetal growth restriction", Thromb Res, 123, pp.55~59 (2008)
- Yee LM, "Mitigating the long-term health risks of adverse pregnancy outcomes", JAMA, 327, pp.421~422 (2022)
- Vodnik T, "Changes in the plasma levels of protein C system parameters in pregnancy", Scand J Clin Lab Invest, 63, pp.481~488 (2003)
- Mahieu B, "Haemostatic changes and acquired activated protein C resistance in normal pregnancy", Blood Coagul Fibrinolysis, 18, pp.685~688 (2007)
- Hansen AT, "Changes in fibrin Ddimer, fibrinogen, and protein S during pregnancy", Scand J Clin Lab Invest, 71, pp.173~176 (2011)
- Takeuchi S, "Evaluation of the plasma protein S dynamics during pregnancy using a total protein S assay : protein S-specific activity decreased from the second trimester", J Obstet Gynaecol Res, 46, pp.376~381 (2020)
- Faught W, "Changes in protein C and protein S levels in normal pregnancy", Am J Obstet Gynecol, 172, pp.147~150 (1995)
- Lefkowitz JB, "Comparison of protein S functional and antigenic assays in normal pregnancy", Am J Obstet Gynecol, 175, pp.657~660 (1996)
- Lutsey PL, "Plasma hemostatic factors and endothelial markers in four racial", ethnic groups : the MESA study, 2006, pp.4, 2629~2635
- Bertina RM, "Mutation in blood coagulation factor V associated with resistance to activated protein C", Nature, 369, pp.64~67 (1994)
- Poort SR, "A common genetic variation in the 3'-untranslated region of the prothrombin gene is associated with elevated plasma prothrombin levels and an increase in venous thrombosis", Blood, 88, pp.3698~3703 (1996)
- Itakura H, "Racial disparities in risk factors for thrombosis", Curr Opin Hematol, 12, pp.364~369 (2005)
- Keenan CR, "The effects of race", ethnicity and sex on the risk of venous thromboembolism, 2007, pp.13, 377~383
- Ceriello A, "Possible role for increased C4b-binding-protein level in acquired protein S deficiency in type I diabetes", Diabetes, 39, pp.447~449 (1990)
- Erem C, "Coagulation and fibrinolysis parameters in type 2 diabetic patients with and without diabetic vascular complications", Med Princ Pract, 14, pp.22~30 (2005)
- Nardozza LM, "Fetal growth restriction : current knowledge", Arch Gynecol Obstet, 295, pp.1061~1077 (2017)
- Uszyński M, "Protein C, protein S, and thrombomodulin in amniotic fluid. A preliminary study", J Perinat Med, 34, pp.289~292 (2006)
- Isermann B, "The thrombomodulin-protein C system is essential for the maintenance of pregnancy", Nat Med, 9, pp.331~337 (2003)
- Gierula M, "Anticoagulant protein S-New insights on interactions and functions", J Thromb Haemost, 18, pp.2801~2811 (2020)
- Preston FE, "Increased fetal loss in women with heritable thrombophilia", Lancet, 348, pp.913~916 (1996)
- Clinical, laboratory standards institute, "Defining, establishing, and verifying reference intervals in clinical laboratory; approved guideline" (2010), Clinical and Laboratory Standards Institute