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Journal of Assisted Reproduction and Genetics

Erschienen in:

01.10.2013 | Genetics

The association between thrombophilic gene mutations and recurrent pregnancy loss

verfasst von: Ahmad Poursadegh Zonouzi, Nader Chaparzadeh, Saeid Ghorbian, Mahzad Mehrzad Sadaghiani, Laya Farzadi, Alieh Ghasemzadeh, Taiebeh Kafshdooz, Masoud Sakhinia, Ebrahim Sakhinia

Erschienen in: Journal of Assisted Reproduction and Genetics | Ausgabe 10/2013

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Abstract

Purpose

To determine whether the Factor V (1691G/A), Factor V HR2 (4070A/G), Prothrombin (20210G/A), PAI-1 (-675 I/D, 5G/4G), ACE (intron 16 I/D), Factor VII (Gln353Arg), Factor XIII (Val34Leu), β-fibrinogen (-455G/A), Glycoprotein Ia (807C/T), tPA (intron 8 D/I) gene mutations could be risk factors for recurrent pregnancy loss (RPL).

Methods

Genotyping of thrombophilic gene mutations were carried out by amplification Refractory Mutation System-PCR (ARMS-PCR) method after DNA extraction.

Results

We found that the mutant allele frequencies of Factor V (1691G/A), Factor V HR2 (4070A/G), Prothrombin (20210G/A), PAI-1 (-675 I/D, 5G/4G), Factor XIII (Val34Leu) and β-fibrinogen (-455G/A) were more seen in the case group compared with the healthy control; However, the difference between the two group is not statistically significant (p > 0.05). Whilst the mutant allele frequencies of other studied genes were lower in the case in comparison to the fertile control women (p > 0.05).

Conclusion

Taken together, our data has shown that the prevalence of thrombophilic gene mutations was similar in women with RPL and healthy controls. Therefore, it appears that further studies on large-scale population and other genetic variants will be needed to conclusively find candidate genes for RPL unknown etiology in the future.

Allison JL, Schust DJ. Recurrent first trimester pregnancy loss: revised definitions and novel causes. Curr Opin Endocrinol Diabetes Obes. 2009;16:446–50.PubMedCrossRef

Altintas A, Pasa S, Akdeniz N, Cil T, Yurt M, Ayyildiz O, et al. Factor V Leiden and G20210A prothrombin mutations in patients with recurrent pregnancy loss: data from the southeast of Turkey. Ann Hematol. 2007;86:727–31.PubMedCrossRef

Berthold H, Guido AH, Jorgen K, Peter H, Holger K, Abdulgabar S. Screening for multiple hereditary hypercoagulability factors using the amplification refractory mutation system. Thromb Res. 2003;111:115–20.CrossRef

Bloomenthal D, Dadelszen P, Liston R, Magee L, Tsang P. The effect of factor V Leiden carriage on maternal and fetal health. CMAJ. 2002;167:48–54.PubMedPubMedCentral

Bom JG, Knijff P, Haverkate F, Bots ML, Meijer P, deJong PTVM, et al. Tissue plasminogen activator and risk of myocardial infarction. Circulation. 1997;95:2623–7.PubMedCrossRef

Brandt JT. Plasminogen and tissue-type plasminogen activator deficiency as risk factors for thromboembolic disease. Arch Pathol Lab Med. 2002;126:1376–81.PubMed

Bray PF. Platelet glycoprotein polymorphisms as risk factors for thrombosis. Curr Opin Hematol. 2000;7:284–9.PubMedCrossRef

Buchholz T, Lohse P, Rogenhofer N, Kosian E, Pihusch R, Thaler CJ. Polymorphisms in the ACE and PAI -1 genes are associated with recurrent spontaneous miscarriages. Hum Reprod. 2003;18:2473–7.PubMedCrossRef

Carp H, Salomon O, Seidman D. Prevalence of genetic markers for thrombophilia in recurrent pregnancy loss. Hum Reprod. 2002;17:1633–7.PubMedCrossRef

10.

Castoldi E, Simioni P, Kalafatis M, Lunghi B, Tormene D, Girelli D, et al. Combinations of 4 mutations (FV R506Q, FV H1299R, FV Y1702C, PT 20210G/A) affecting the prothrombinase complex in a thrombophilic family. Blood. 2000;96:1443–8.PubMed

11.

Cleary-Goldman J, Nakhuda GS, Zimmermann RC, Sauer MV. The role of factor V Leiden mutation in recurrent pregnancy loss. J Am Med Wom Assoc. 2003;58:165–72.PubMed

12.

Coulam CB, Jeyendran RS, Fishel LA, Roussev R. Multiple thrombophilic gene mutations rather than specific gene mutations are risk factors for recurrent miscarriage. Am J Reprod Immunol. 2006;55:360–8.PubMedCrossRef

13.

Coulam CB, Wallis D, Weinstein J, DasGupta DS, Jeyendran RS. Comparison of thrombophilic gene mutations among patients experiencing recurrent miscarriage and deep vein thrombosis. Am J Reprod Immunol. 2008;60:426–31.PubMedCrossRef

14.

Dawood F, Mountford R, Farquharson R, Quenby S. Genetic polymorphisms on the factor V gene in women with recurrent miscarriage and acquired APCR. Hum Reprod. 2007;22:2546–53.PubMedCrossRef

15.

Dossenbach-Glaninger A, Trotsenburg M, Dossenbach M, Oberkanins C, Moritz A, Krugluger W, 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.PubMedCrossRef

16.

Dunne FM, Doggen CJ, Heemskerk M, Rosendaal FR, Helmerhorst FM. Factor V Leiden mutation in relation to fecundity and miscarriage in women with venous thrombosis. Hum Reprod. 2005;20:802–6.PubMedCrossRef

17.

Ford HB, Schust DJ. Recurrent pregnancy loss: etiology, diagnosis, and therapy. Rev Obstet Gynecol. 2009;2:76–83.PubMedPubMedCentral

18.

Garcia-Enguidanos A, Calle ME, Valero J, Luna S, Dominguez-Rojas V. Risk factors in miscarriage: a review. Eur J Obstet Gynecol Reprod Biol. 2002;102:111–9.PubMedCrossRef

19.

Ghee CB, Burrows RF. Prothrombin G20210A mutation is not associated with recurrent miscarriages. Aust N Z J Obstet Gynaecol. 2002;42:167–9.PubMedCrossRef

20.

Goodman CS, Coulam CB, Jeyendran RS, Acosta VA, Roussev R. Which thrombophilic gene mutations are risk factors for recurrent pregnancy loss? Am J Reprod Immunol. 2006;56:230–6.PubMedCrossRef

21.

Goodman C, Hur J, Goodman CS, Jeyendran RS, Coulam C. Are polymorphisms in the ACE and PAI-1 genes associated with recurrent spontaneous miscarriages? Am J Reprod Immunol. 2009;62:365–70.PubMedCrossRef

22.

Gumpel C, Fornasiero L, Suarez S, Santillan G, Colabianchi J. PAI- 1 4G⁄ 5G polymorphism detection and obstetric complications. Thromb Res. 2009;123:S148.CrossRef

23.

Hashimoto K, Shizusawa Y, Shimoya K. The factor V Leiden mutation in Japanese couples with recurrent spontaneous abortion. Hum Reprod. 1999;14:1872–4.PubMedCrossRef

24.

Humphries SE, Cook M, Dubovitz M, Stirling Y, Meade TW. Role of genetic variation at the fibrinogen locus in determination of plasma fibrinogen concentrations. Lancet. 1987;1:1452–5.PubMedCrossRef

25.

Jaleh Z, Mozhdeh M, Khatereh A, Fariborz G, Zohreh T. The value of hysteroscopy in diagnosis of chronic endometritis in patients with unexplained recurrent spontaneous abortion. Eur J Obstet Gynecol Reprod Biol. 2011;155:217–20.CrossRef

26.

Jeddi-Tehrani M, Torabi R, Zarnani AH, Mohammadzadeh A, Arefi S, Zeraati H, et al. Analysis of plasminogen activator inhibitor-1, integrin beta3, beta fibrinogen, and methylenetetrahydrofolate reductase polymorphisms in Iranian women with recurrent pregnancy loss. Am J Reprod Immunol. 2011;66:149–56.PubMedCrossRef

27.

Kupferminc MJ. Thrombophilia and pregnancy. Reprod Biol Endocrinol. 2003;1:111–33.PubMedCrossRefPubMedCentral

28.

Marty S, Barro C, Chatelain B, Fimbel B, Tribout B, Reynaud J, et al. The paradoxical association between inherited factor VII deficiency and venous thrombosis. Haemophilia. 2008;14:564–70.PubMedCrossRef

29.

Meka A, Reddy BM. Recurrent spontaneous abortions: an overview of genetic and non-genetic backgrounds. Int J Hum Genet. 2006;6:109–17.

30.

Okumus G, Kiyan E, Arseven O, Tabak L, Bayrak EK, Unaltuna NE, et al. Platelet glycoprotein ia 807c/t and 873g/a polymorphisms in patients with venous thromboembolism. Clin Appl Thromb Hemost. 2007;13:101–3.PubMedCrossRef

31.

Pandey MK, Rani R, Agrawal S. An update in recurrent spontaneous abortion. Arch Gynecol Obstet. 2005;272:95–108.PubMedCrossRef

32.

Reiner AP, Siscovick DS, Rosendaal FR. Platelet glycoprotein gene polymorphisms and risk of thrombosis: facts and fancies. Rev Clin Exp Hematol. 2001;5:262–87.PubMedCrossRef

33.

Ridker PM, Baker MT, Hennekens CH, Stampfer MJ, Vaughn DE. Alu-repeat polymorphism in the gene coding for tissue-type plasminogen activator (TPA) and risks of myocardial infarction among middle-aged men. Arterioscler Thromb Vasc Biol. 1997;17:1687–90.PubMed

34.

Rousseau F, Rehel R, Rouillard P, DeGranpre P, Khandjian EW. High throughput and economical mutation detection and RFLP analysis using a minimethod for DNA preparation from whole blood and acrylamide gel electrophoresis. Hum Mutat. 1994;4:51–4.PubMedCrossRef

35.

Sehirali S, Inal MM, Yildirim Y, Balim Z, Kosova B, Karamizrak T, et al. Prothrombin G20210A mutation in cases with recurrent miscarriage: a study of the Mediterranean population. Arch Gynecol Obstet. 2005;273:170–3.PubMedCrossRef

36.

Seremak-Mrozikiewicz A, Drews K, Kurzawińska G, Barlik M, Mrozikiewicz PM. The connection between Arg353Gln polymorphism of coagulation factor VII and recurrent miscarriages. Ginekol Pol. 2009;80:8–13.PubMed

37.

Steeds R, Adams M, Smith P, Channer K, Samani NJ. Distribution of tissue plasminogen activator insertion/deletion polymorphism in myocardial infarction and control subjects. Thromb Haemost. 1998;79:980–4.PubMed

38.

Subrt I, Ulcova-Gallova Z, Cerna M, Hejnalova M, Slovanova J, Bibkova K, et al. Recurrent pregnancy loss, plasminogen activator inhibitor-1 (-675) 4G/5G polymorphism and antiphospholipid antibodies in Czech women. Am J Reprod Immunol. 2013. doi:10.1111/aji.12099.PubMed

39.

Walker ID. Thrombophilia in pregnancy. J Clin Pathol. 2000;53:573–80.PubMedCrossRefPubMedCentral

40.

Yenicesu I, Cetin M, Ozdemir O, Cetin A, Ozen F, Yenicesu C, et al. A prospective case–control study analyzes 12 thrombophilic gene mutations in Turkish couples with recurrent pregnancy loss. Am J Reprod Immunol. 2010;63:126–36.PubMedCrossRef

Titel: The association between thrombophilic gene mutations and recurrent pregnancy loss
verfasst von: Ahmad Poursadegh Zonouzi
Nader Chaparzadeh
Saeid Ghorbian
Mahzad Mehrzad Sadaghiani
Laya Farzadi
Alieh Ghasemzadeh
Taiebeh Kafshdooz
Masoud Sakhinia
Ebrahim Sakhinia
Publikationsdatum: 01.10.2013
Verlag: Springer US
Erschienen in: Journal of Assisted Reproduction and Genetics / Ausgabe 10/2013
Print ISSN: 1058-0468
Elektronische ISSN: 1573-7330
DOI: https://doi.org/10.1007/s10815-013-0071-5

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The association between thrombophilic gene mutations and recurrent pregnancy loss