Annals of Hematology

, Volume 85, Issue 4, pp 268–271 | Cite as

Thrombophilic mutations in Iranian patients with infertility and recurrent spontaneous abortion

  • Reza Behjati
  • Mohammad Hossein Modarressi
  • Mahmood Jeddi-Tehrani
  • Pouneh Dokoohaki
  • Jamileh Ghasemi
  • Amir Hassan Zarnani
  • Mahmoud Aarabi
  • Toktam Memariani
  • Marefat Ghaffari
  • Mehdi A. Akhondi
Original Article

Abstract

Factor V Leiden (FVL) G1691A, methylenetetrahydrofolate reductase (MTHFR) C677T, and factor II (FII) G20210A mutations are three important causes of thrombophilia, the condition that might be related to infertility and recurrent spontaneous abortion (RSA). In this study we evaluated the presence of these three mutations in 36 female patients with unexplained infertility, 65 female patients with unexplained RSA, and 62 healthy fertile women as control group. DNA was extracted from peripheral blood samples and PCR-RFLP was performed for the molecular diagnosis of each mutation. In addition, activated protein C resistance (APC-R) was also evaluated. The frequencies of FVL, MTHFR, and FII mutations (heterozygous and homozygous) in the control group were 0.0%, 38.7%, and 3.2%, respectively. The frequency of FVL mutation in patients with infertility (30.6%) or RSA (20.0%) was significantly higher than that of the control group. A significantly higher MTHFR mutation rate was also observed in patients with RSA (63.1%) as compared to controls. However, the mutation rate of MTHFR in patients with infertility (50.0%) was not statistically different from that in controls. No significant difference was observed in the frequencies of FII mutations between the patients and controls. Decreased levels of APC-R were observed in 25.0% of infertile patients and 18.9% of patients with RSA. In conclusion, our results show a skew towards higher mutation frequencies of FVL and MTHFR in patients that may necessitate detection of such mutations in these Iranian patients.

Keywords

Factor V Leiden Methylenetetrahydrofolate reductase Factor II Thrombophilia Recurrent spontaneous abortion Infertility 

Notes

Acknowledgement

We would like to express our sincerest appreciation to Dr. Akhondi as the chairman of Avesina Research Institute for his kindness in providing all of the expenses of this project.

References

  1. 1.
    Kovalevsky G, Gracia CR, Berlin JA, Sammel MD, Barnhart KT (2004) Evaluation of the association between hereditary thrombophilias and recurrent pregnancy loss: a meta-analysis. Arch Intern Med 164(5):558−563CrossRefPubMedGoogle Scholar
  2. 2.
    Lane DA, Mannucci PM, Bauer KA, Bertina RM, Bochkov NP, Boulyjenkov V et al (1996) Inherited thrombophilia: part 1. Thromb Haemost 76:651−662PubMedGoogle Scholar
  3. 3.
    Lane DA, Mannucci PM, Bauer KA, Bertina RM, Bochkov NP, Boulyjenkov V et al (1996) Inherited thrombophilia: part 2. Thromb Haemost 76:824−834PubMedGoogle Scholar
  4. 4.
    De Stefano V, Finazzi G, Mannucci PM. (1996) Inherited thrombophilia: pathogenesis, clinical syndromes, and management. Blood 87:3531−3544PubMedGoogle Scholar
  5. 5.
    Vefring H, Lie RT, ODegard R, Mansoor MA, Nilsen ST (2004) Maternal and fetal variants of genetic thrombophilias and the risk of preeclampsia. Epidemiology 15(3):317−322CrossRefPubMedGoogle Scholar
  6. 6.
    Wisotzkey JD, Bayliss P, Rutherford E, Bell T (1999) Placental genotyping of the factor V Leiden, prothrombin 20210A and the methylenetetrahydrofolate reductase (MTHFR) C677T alleles in IUGR pregnancies. Thromb Haemost 81(5):844−845PubMedGoogle Scholar
  7. 7.
    Zoller B, Svensson PJ, He X, Dahlback B (1994) Identification of the same factor V gene mutation in 47 out of 50 thrombosis-prone families with inherited resistance to activated protein C. J Clin Invest 94:2521−2524PubMedCrossRefGoogle Scholar
  8. 8.
    Major DA, Sane DC, Herrington DM (2000) Cardiovascular implications of the factor V Leiden mutation. Am Heart J 140(2):189−195CrossRefPubMedGoogle Scholar
  9. 9.
    Candito M, Magnaldo S, Bayle J, Dor JF, Gillet Y, Bongain A et al (2003) Clinical B12 deficiency in one case of recurrent spontaneous pregnancy loss. Clin Chem Lab 41(8):1026−1027CrossRefGoogle Scholar
  10. 10.
    Poort SR, Rosendaal FR, Reitsma PH, Bertina RM (1996) 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 88:3698−3703PubMedGoogle Scholar
  11. 11.
    Prandoni P, Lensing AWA, Cogo A, Cuppini S, Villalta S, Carta M et al (1996) The long-term clinical course of acute deep venous thrombosis. Ann Intern Med 125:1−7PubMedGoogle Scholar
  12. 12.
    Van den Belt AGM, Sanson BJ, Simioni P, Prandoni P, Buller HR, Girolami A et al (1997) Recurrence of venous thromboembolism in patients with familial thrombophilia. Arch Intern Med 157:2227−2232CrossRefPubMedGoogle Scholar
  13. 13.
    Sarig G, Younis JS, Hoffman R, Lanir N, Blumenfeld Z, Brenner B (2002) Thrombophilia is common in women with idiopathic pregnancy loss and is associated with late pregnancy wastage. Fertil Steril 77(2):342−347CrossRefPubMedGoogle Scholar
  14. 14.
    Finan RR, Tamim H, Ameen G, Sharida HE, Rashid M, Almawi WY (2002) Prevalence of factor V G1691A (factor V-Leiden) and prothrombin G20210A gene mutations in a recurrent miscarriage population. Am J Hematol 71(4):300−305CrossRefPubMedGoogle Scholar
  15. 15.
    Rand JH, Luong TH (1999) Thrombophilias: diagnosis and treatment of thrombophilia relating to contraception and pregnancy. Semin Hematol 36:2−9PubMedGoogle Scholar
  16. 16.
    Rosendaal FR (1999) Venous thrombosis: a multicausal disease. Lancet 353:1167−1173CrossRefPubMedGoogle Scholar
  17. 17.
    Frosst P, Blom HJ, Milos R, Goyette P, Sheppard CA, Matthews RG et al (1995) A candidate genetic risk factor for vascular disease: a common mutation in methylenetetrahydrofolate reductase. Nat Genet 10(1):111−113CrossRefPubMedGoogle Scholar
  18. 18.
    Morita H, Kurihara H, Tsubaki S, Sugiyama T, Hamada C, Kurihara Y et al (1998) Methylenetetrahydrofolate reductase gene polymorphism and ischemic stroke in Japanese. Arterioscler Thromb Vasc Biol 18(9):1465−1469PubMedGoogle Scholar
  19. 19.
    Adjalla CE, Amouzou EK, Sanni A, Abdelmouttaleb I, Chabi NW, Namour F et al (2003) Low frequency of mutated methylenetetrahydrofolate reductase 677C-->T and 1298A-->C genetics single nucleotide polymorphisms (SNPs) in Sub-Saharan populations. Clin Chem Lab Med 41(8):1028−1032CrossRefPubMedGoogle Scholar
  20. 20.
    Rousseau F, Rehel R, Rouillard P, DeGranpre P, Khandjian EW (1994) High throughput and economical mutation detection and RFLP analysis using a minimethod for DNA preparation from whole blood and acrylamide gel electrophoresis. Hum Mutat 4(1):51−54CrossRefPubMedGoogle Scholar
  21. 21.
    Pauler HU, Voigt-Tschirschwitz T, Hinney B, Burfeind P, Wolf C, Emons G (2003) Analyzes of three common thrombophilic gene mutations in German women with recurrent abortions. Acta Obstet Gynecol Scand 82:942−947CrossRefPubMedGoogle Scholar
  22. 22.
    Zeinali S, Duca F, Zarbakhsh B, Tagliabue L, Mannucci PM (2000) Thrombophilic mutations in Iran. Thromb Haemost 83(2):351−352PubMedGoogle Scholar
  23. 23.
    Souza SS, Ferriani RA, Pontes AG, Zago MA, Franco RF (1999) Factor V leiden and factor II G20210A mutations in patients with recurrent abortion. Hum Reprod 14(10):2448−2450CrossRefPubMedGoogle Scholar
  24. 24.
    Glueck CJ, Wang P, Goldenberg N, Sieve L (2004) Pregnancy loss, polycystic ovary syndrome, thrombophilia, hypofibrinolysis, enoxaparin, metformin. Clin Appl Thromb Hemost 10(4):323−334PubMedCrossRefGoogle Scholar
  25. 25.
    Hashimoto K, Shizusawa Y, Shimoya K, Ohashi K, Shimizu T, Azuma C et al (1999) The factor V Leiden mutation in Japanese couples with recurrent spontaneous abortion. Hum Reprod 14(7):1872−1874CrossRefPubMedGoogle Scholar
  26. 26.
    Golbahar J, Hamidi A, Aminzadeh MA, Omrani GR (2004) Association of plasma folate, plasma total homocysteine, but not methylenetetrahydrofolate reductase C667T polymorphism, with bone mineral density in postmenopausal Iranian women: a cross-sectional study. Bone 35(3):760−765CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag 2006

Authors and Affiliations

  • Reza Behjati
    • 1
  • Mohammad Hossein Modarressi
    • 1
    • 2
    • 4
  • Mahmood Jeddi-Tehrani
    • 3
  • Pouneh Dokoohaki
    • 3
  • Jamileh Ghasemi
    • 1
  • Amir Hassan Zarnani
    • 3
  • Mahmoud Aarabi
    • 1
  • Toktam Memariani
    • 1
  • Marefat Ghaffari
    • 1
  • Mehdi A. Akhondi
    • 1
  1. 1.Reproductive Biology, Biotechnology and Infertility Research CenterAvesina Research InstituteTehranIran
  2. 2.Department of Medical GeneticsTehran University of Medical SciencesTehranIran
  3. 3.Monoclonal Antibody Research CenterAvesina Research InstituteTehranIran
  4. 4.Department of Genetics and InfertilityAvesina Research InstituteTehranIran

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