Retrospective Investigation of Prothrombin, MTHFR, FV Leiden and PAI-1 Polymorphisms in Recurrent Abortion in the Southeastern Anatolia Region

Abstract

Objective: Recurrent pregnancy loss (RPL) is defined as the loss of two or more gestations before the 20th gestational week. Approximately half of the factors that cause RPL are idiopathic, and immunologic, endocrinological and anatomical causes are the most important among known causes. Genetic causes account for 2-5% of the factors that cause RPL and it is known that hereditary thrombophilia are found in the genetic background of the losses in the advanced gestational weeks.
Methods: In this study, MTHFR, FV-Leiden, PAI-1 and Prothrombin polymorphisms of 1395 patients without any chromosomal anomalies were investigated retrospectively for the cause of recurrent pregnancy loss.
Findings: Hereditary thrombophilia polymorphisms were investigated with heterozygous, homozygous and wild type percentage slices.
Conclusion:The results are discussed in the light of current knowledge and in the context of regional data. 

Keywords

• Prothrombin
• MTHFR
• PAI-1
• trombophilia
• recurrent pregnancy loss

Güneydoğu Anadolu Bölgesi’ndeki Tekrarlayan Abortus Olgularında Protrombin, MTHFR, FV Leiden ve PAI-1 Polimorfizmlerinin Retrospektif Olarak İncelenmesi

Abstract

Amaç: Tekrarlayan gebelik kaybı (TGK), 20. gebelik haftasından önce meydana gelen iki ve ya daha fazla gebelik kaybı olarak tanımlanır. TGK’na yol açan faktörlerin yaklaşık yarısı idiopatiktir, bilinen nedenler içinde ise immünolojik, endokrinolojik ve anatomik nedenler en önemlileridir. TGK’na yol açan faktörler içinde genetik nedenler %2-5 oranında yer tutmakta ve ilerleyen gebelik haftalarındaki genetik nedenli gebelik kayıplarının kalıtsal trombofili nedenleri ile olduğu bilinmektedir.

Yöntemler: Bu çalışmada tekrarlayan gebelik kayıpları nedeni ile araştırılan, herhangi bir kromozom anomalisi olmayan 1395 hastanın MTHFR, FV-Leiden, PAI-1 ve Protrombin polimorfizmleri retrospektif olarak incelenmiştir.

Bulgular: Kalıtsal trombofili polimorfizmleri heterozigot, homozigot ve yabanıl olarak yüzdelik dilimlerle incelenmiştir.

Sonuç: Çıkan sonuçlar güncel bilgiler ışığında ve bölgesel veriler eşliğinde tartışılmıştır. 

Keywords

• Protrombin
• MTHFR
• PAI-1
• trombofili

References

1. 1. Kolte AM, Bernardi LA, Christiansen OB, et al. Terminology for pregnancy loss prior to viability: a consensus statement from the ESHRE early pregnancy special interest group. Hum Reprod. 2015; 30: 495-8.
2. 2. Stephenson M, Kutteh W. Evaluation and Management of Recurrent Early Pregnancy Loss. Clin Obstet Gynecol. 2007; 50: 132-45.
3. 3. Jauniaux E, Farquharson RG, Christiansen OB, Exalto N. Evidence-based guidelines for the investigation and medical treatment of recurrent miscarriage. Hum Reprod. 2006; 21: 2216-22.
4. 4. Greer IA. Thrombophilia: implications for pregnancy outcome. Thromb Res. 2003; 109: 73-81.
5. 5. Regan L, Braude PR, Trembath PL. Influence of past reproductive performance on risk of spontaneous abortion. BMJ. 1989; 299: 541-5.
6. 6. Pitas RE, Boyles JK, Lee SH, Foss D, Mahley RW. Astrocytes synthesize apolipoprotein E and metabolize apolipoprotein E-containing lipoproteins. Biochim Biophys Acta (BBA)/Lipids Lipid Metab. 1987; 917: 148-61.
7. 7. Li TC, Makris M, Tomsu M, Tuckerman E, Laird S. Recurrent miscarriage: aetiology, management and prognosis. Hum Reprod Update. 2002; 8: 463-81.
8. 8. American College of Obstetricians and Gynecologists. ACOG practice bulletin. Management of recurrent pregnancy loss. Int J Gynaecol Obstet. 2002; 78: 179-90.

9. 9. Katz V, Kuller J. Recurrent Miscarriage. Am J Perinatol. 1994; 11: 386-97.
10. 10. Buchholz T, Thaler CJ. Inherited Thrombophilia: Impact on Human Reproduction. Am J Reprod Immunol. 2003; 50: 20-32.
11. 11. İzmirli M, Aldemir Ö, Gögebakan B, Alptekin D. The studies about diseases concerning with contemplated MTHFR 677 C>T polymorphism. Dicle Med Journal/Dicle Tıp Derg. 2014; 41: 244-56.
12. 12. Wu X, Zhao L, Zhu H, He D, Tang W, Luo Y. Association Between the MTHFR C677T Polymorphism and Recurrent Pregnancy Loss: A Meta-Analysis. Genet Test Mol Biomarkers. 2012; 16: 806-11.
13. 13. Sergi C, Al Jishi T, Walker M. Factor V Leiden mutation in women with early recurrent pregnancy loss: a meta-analysis and systematic review of the causal association. Arch Gynecol Obstet. 2015; 291: 671-9. 14. Gerhardt A, Scharf RE, Beckmann MW, et al. Prothrombin and Factor V Mutations in Women with a History of Thrombosis during Pregnancy and the Puerperium. N Engl J Med. 2000; 342: 374-80.
14. 15. Salazar Garcia MD, Sung N, Mullenix TM, et al. Plasminogen Activator Inhibitor-1 4G/5G Polymorphism is Associated with Reproductive Failure: Metabolic, Hormonal, and Immune Profiles. Am J Reprod Immunol. 2016; 76: 70-81.
15. 16. Kujovich JL. Thrombophilia and pregnancy complications. Am J Obstet Gynecol. 2004; 191: 412-24.
16. 17. Rey E, Kahn SR, David M, Shrier I. Thrombophilic disorders and fetal loss: a meta-analysis. Lancet. 2003; 361: 901-8.
17. 18. Foka ZJ, Lambropoulos AF, Saravelos H, et al. Factor V leiden and prothrombin G20210A mutations, but not methylenetetrahydrofolate reductase C677T, are associated with recurrent miscarriages. Hum Reprod. 2000; 15: 458-62.
18. 19. Incebiyik A, Hilali NG, Camuzcuoglu A, et al. Prevalence of thromogenic gene mutations in women with recurrent miscarriage: A retrospective study of 1,507 patients. Obstet Gynecol Sci. 2014; 57: 513-7.
19. 20. Friedline JA, Ahmad E, Garcia D, et al. Combined factor V Leiden and prothrombin genotyping in patients presenting with thromboembolic episodes. Arch Pathol Lab Med. 2001; 125: 105-11.
20. 21. Bilici M, Öz İİ, İlikhan SU, et al. The predictive value of factor V Leiden, prothrombin G20210A and MTHFR C677T Gene mutations on the location of venous thromboembolism. Dicle Med J / Dicle Tip Derg. 2015; 42: 467-71.
21. 22. Ayyildiz O, Kalkanli S, Batun S, et al. Prothrombin G20210A gene mutation with LightCycler polymerase chain reaction in venous thrombosis and healthy population in the southeast of Turkey. Heart Vessels. 2004; 19: 164-6.
22. 23. Cripe LD, Moore KD, Kane WH. Structure of the gene for human coagulation factor V. Biochemistry. 1992; 31: 3777-85.
23. 24. Özen F, Koçak N, Ejder Yıldırım M, et al. Sivas Populasyonunda Faktör V Genin Leiden (G1691a) ve Hr2 (A4070g) Polimorfizmleri. İnönü Üniversitesi Tıp Fakültesi Derg. 2009; 16: 179-83.
24. 25. Dossenbach-Glaninger A, van Trotsenburg M, Dossenbach M, et al. Plasminogen activator inhibitor 1 4G/5G polymorphism and coagulation factor XIII Val34Leu polymorphism: impaired fibrinolysis and early pregnancy loss. Clin Chem. 2003; 49: 1081-6. 26. Ejder Yıldırım M, Dağ Ş, Küçük Kurtulgan H, et al. Plazminojen aktivatör inhibitör-1 (PAI-1) 4G/4G polimorfizminin gebelik kayıplarıyla ilişkisi The association of plasminogen activator inhibitor-1 (PAI1) 4G/4G polymorphism with miscarriages. Cumhur Tıp Derg/Cumhur Med J. 2014; 36: 350-5.
25. 27. Bayram B, Kılıççı Ç, Bozarı S, Onlu H, Sahin F. Muş İlinde Tekrarlayan Gebelik Kayıpları İle Mthfr C677t ve A1298c ve Pai-1 4g/5g Polimorfizmleri Arasındaki İlişki ve Alel rekansları. Kocatepe Tıp Derg. 2015; 12: 61-7.