Tekrarlayan Gebelik Kaybı ve Kendiliğinden Düşük Yaşayan Kadınlarda FXIII Val34Leu ve PAI 4G/5G Polimorfizmlerinin Karşılaştırmalı Değerlendirilmesi

Yıl 2025, Cilt: 6 Sayı: 2, 159 - 163, 28.07.2025

Ayça Kocaağa , Ece Akca Salık

Öz

Giriş: Trombofili, tromboza eğilimi artıran, edinilmiş veya kalıtsal olabilen bir durumdur. Gebelikte trombofili preeklampsi, intrauterin büyüme geriliği ve düşük gibi çeşitli komplikasyonlara yol açabilir. Bu çalışmanın amacı, spontan ve tekrarlayan gebelik kaybında (TGK) FXIII Val34Leu ve PAI 4G/5G polimorfizmi arasındaki ilişkiyi karşılaştırmalı olarak araştırmaktır.

Yöntemler: Bu vaka-vaka çalışmasına 408 TGK tanılı kadın ve 128 spontan abort (SA) ve benzer aile öyküsü tanılı kadın olmak üzere toplam 536 kişi katıldı. Bu varyantların genotip ve alel frekanslarını ve iki grup arasındaki anlamlılığı istatistiksel olarak araştırmak için SPSS-22 kullanıldı.

Bulgular: TGK ve SA hastalarının ortalama yaşları sırasıyla 29,50 ± 5,46 ve 30,02 ± 6,03 yıldı. Her iki grupta en sık görülen varyant Val/Val iken, en az görülen varyant Leu/Leu FXIII Val34Leu idi. Leu/Leu FXIII Val34Leu varyantı için TGK ve SA hastaları arasında genotip ve alel dağılımları açısından anlamlı bir fark yoktu (p=0,167 ve 0,174). SA ve TGK grupları arasında PAI-1 4G/5G polimorfizminin genotip ve alel frekansları açısından anlamlı bir fark gözlenmedi (p=0,110 ve 0,092). Spontan düşük öyküsü olan hastalarda PAI 4G/4G ve FXIII Val/Val kombine mutasyonları (%23,4) TGK hastalarına (%21,0) göre daha baskındı.

Sonuç: Her iki grupta plazminojen aktivatör inhibitörü-1 4G/4G ve FXIII Val/Val genetik varyantlarının sıklığı ve kombinasyonu açısından anlamlı bir fark bulunmaması, bu varyantların hem tekrarlayan gebelik kaybı olan hem de tek düşük yapan kadın hastalarda önemli olabileceğini göstermektedir.

Anahtar Kelimeler

FXIII Val34Leu , PAI-1 4G/5G , tekrarlayan gebelik kaybı , spontan düşük , trombofili.

Comparative Evaluation of FXIII Val34Leu and PAI 4G/5G Polymorphisms in Women with Recurrent Pregnancy loss and spontaneous miscarriage

Öz

Introduction: Thrombophilia is a condition that increases the tendency to thrombosis and can be acquired or hereditary. If thrombophilia is present during pregnancy, it can lead to various complications such as preeclampsia, intrauterine growth retardation and miscarriage. The aim of this study was to comparatively investigate the association between FXIII Val34Leu and PAI 4G/5G polymorphism in spontaneous and recurrent pregnancy loss (RPL).

Methods: A total of 536 people participated in this case-case study, including 408 women diagnosed with RPL and 128 women diagnosed with spontaneous abortion (SA) with a similiar family history. SPSS-22 was used to statistically investigate the genotype and allele frequencies of these variants and the significance between the two groups.

Results: The mean age of the RPL and SA patients was 29.50 ± 5.46 and 30.02±6.03 years, respectively. The most common variant in both groups was Val/Val, while the least common variant was Leu/Leu FXIII Val34Leu. There was no significant difference in genotype and allele distributions for the Leu/Leu FXIII Val34Leu variant between RPL and SA patients (p=0.167 and 0.174). In our study, no significant difference was observed between SA and RPL groups in terms of genotype and allele frequencies of PAI-1 4G/5G polymorphism (p=0.110 and 0.092). PAI 4G/4G and FXIII Val/Val double mutations were dominant in patients with spontaneous abortion (23.4%) compared to RPL patients (21.0%).

Conclusions: The absence of a significant difference in the frequency and combination of plasminogen activator inhibitor-1 4G/4G and FXIII Val/Val genetic variants in both groups suggests that these variants are important both in patients with recurrent pregnancy loss and in patients with a spontaneous abortion.

Anahtar Kelimeler

FXIII Val34Leu , PAI-1 4G/5G , recurrent pregnancy loss , spontaneous abortion , thrombophilia.

Etik Beyan

The study protocol was approved by the ethical committee of Eskisehir City Hospital (Protocol Number: ESH/BAEK/2025/134).

Kaynakça

• Turesheva A, Aimagambetova G, Ukybassova T, et al. Recurrent Pregnancy Loss Etiology, Risk Factors, Diagnosis, and Management. Fresh Look into a Full Box. J Clin Med. 2023;12(12):4074.
• Li Q, Chen S, Dong X, et al. The Progress of Research on Genetic Factors of Recurrent Pregnancy Loss. Genet Res (Camb). 2023;2023:9164374.
• Salvagno GL, Lippi G, Franchini M, et al. The cost-benefit ratio of screening pregnant women for thrombophilia. Blood Transfus. 2007;5(4):189-203.
• Cho KH, Kim BC, Kim MK, Shin BA. No association of factor XIII Val34Leu polymorphism with primary intracerebral hemorrhage and healthy controls in Korean population. J Korean Med Sci. 2002;17(2):249-53.
• Sajjadi SM, Khosravi A, Pakravesh J, et al. Factor XIII Val34Leu polymorphism and risk of recurrent pregnancy loss in Iranian population: a case control study. Frontiers in Biology. 2016;11(6):471-5.
• Ariëns RA, Philippou H, Nagaswami C, Weisel JW, Lane DA, Grant PJ. The factor XIII V34L polymorphism accelerates thrombin activation of factor XIII and affects cross-linked fibrin structure. Blood. 2000;96(3):988-95.
• Elbaz A, Poirier O, Canaple S, Chédru F, Cambien F, Amarenco P. The association between the Val34Leu polymorphism in the factor XIII gene and brain infarction. Blood. 2000;95(2):586-91.
• Binder BR, Christ G, Gruber F, et al. Plasminogen activator inhibitor 1: physiological and pathophysiological roles. News Physiol Sci. 2002;17:56-61.
• Muetze S, Eggermann T, Leeners B, et al. The 4G/5G polymorphism in the plasminogen activator inhibitor-1 gene is not associated with HELLP syndrome. J Thromb Thrombolysis. 2009;27(2):141-5.
• Maghsudlu M, Noroozi Z, Zokaei E, Motevaseli E. Systematic review and meta-analysis of association between plasminogen activator inhibitor-1 4G/5G polymorphism and recurrent pregnancy loss: an update. Thromb J. 2024;22(1):44.
• Gumus E. Güneydoğu Anadolu Bölgesi’ndeki Tekrarlayan Abortus Olgularında Protrombin, MTHFR, FV Leiden ve PAI-1 Polimorfizmlerinin Retrospektif Olarak İncelenmesi. Dicle Medical Journal. 2018;45(3):275-81.
• Marquard K, Westphal LM, Milki AA, Lathi RB. Etiology of recurrent pregnancy loss in women over the age of 35 years. Fertil Steril. 2010;94(4):1473-7.
• Abu-Heija A. Thrombophilia and Recurrent Pregnancy Loss: Is heparin still the drug of choice? Sultan Qaboos Univ Med J. 2014;14(1):e26-36.
• Corral J, González-Conejero R, Iniesta JA, Rivera J, Martínez C, Vicente V. The FXIII Val34Leu polymorphism in venous and arterial thromboembolism. Haematologica. 2000;85(3):293-7.
• Barbosa HC, Carvalho EC, Barini R, Siqueira LH, Costa DS, Annichino-Bizzacchi JM. Tyr204Phe and Val34Leu polymorphisms in two Brazilian ethnic groups and in patients with recurrent miscarriages. Fertil Steril. 2004;82(5):1455-7.
• Elmahgoub IR, Afify RA, Abdel Aal AA, El-Sherbiny WS. Prevalence of coagulation factor XIII and plasminogen activator inhibitor-1 gene polymorphisms among Egyptian women suffering from unexplained primary recurrent miscarriage. J Reprod Immunol. 2014;103:18-22.
• Ariëns RA, Lai TS, Weisel JW, Greenberg CS, Grant PJ. Role of factor XIII in fibrin clot formation and effects of genetic polymorphisms. Blood. 2002;100(3):743-54.
• López Ramírez Y, Vivenes M, Miller A, et al. Prevalence of the coagulation factor XIII polymorphism Val34Leu in women with recurrent miscarriage. Clin Chim Acta. 2006;374(1-2):69-74.
• Kim SD, Hwang JK, Park SC, et al. Prevalence of the Factor XIII Val34Leu Polymorphism in Korean Patients with Deep Vein Thrombosis. Ann Vasc Surg. 2016;32:57-64.
• Wells PS, Anderson JL, Scarvelis DK, Doucette SP, Gagnon F. Factor XIII Val34Leu variant is protective against venous thromboembolism: a HuGE review and meta-analysis. Am J Epidemiol. 2006;164(2):101-9.
• Sarecka-Hujar B, Łoboda D, Paradowska-Nowakowska E, Gołba KS. Coagulation Factor XIII Val34Leu Polymorphism in the Prediction of Premature Cardiovascular Events-The Results of Two Meta-Analyses. J Clin Med. 2022;11(12):3454.
• Bagheri M, Rad IA, Omrani MD, Nanbaksh F. The Val34Leu genetic variation in the A subunit of coagulation factor XIII in recurrent spontaneous abortion. Syst Biol Reprod Med. 2011;57(5):261-4.
• Jung JH, Kim JH, Song GG, Choi SJ. Association of the F13A1 Val34Leu polymorphism and recurrent pregnancy loss: A meta-analysis. Eur J Obstet Gynecol Reprod Biol. 2017;215:234-40.
• Kattula S, Bagoly Z, Tóth NK, Muszbek L, Wolberg AS. The factor XIII-A Val34Leu polymorphism decreases whole blood clot mass at high fibrinogen concentrations. J Thromb Haemost. 2020;18(4):885-94.
• Ranellou K, Paraskeva A, Kyriazopoulos P, Batistatou A, Evangelou A, El-Aly M, et al. Polymorphisms in prothrombotic genes in young stroke patients in Greece: a case-controlled study. Blood Coagul Fibrinolysis. 2015;26(4):430-5.
• Shaala I, Deghady A, Elwafa R, Hosny T, Ammar E. Detection of plasminogen activator inhibitor-1 (-675 4G/5G) gene polymorphism in women with recurrent abortion. Hematology & Transfusion International Journal. 2019;7:41-4.