Journal of Kerman University of Medical Sciences

The Association between Preeclampsia and Defined Polymorphisms in Prothrombin and Coagulation Factor V Genes

Document Type : Original Article

Authors

Zohreh Salari 1
Nasrollah Saleh-gohari 2
Nushin Zainali 3
Neda Salmani-Cheharfarsakhi 4

1 Associate Professor of Obstetrics & Genecology, Afzalipour School of Medicine & Physiology Research Center, Kerman University of Medical Sciences, Kerman, Iran

2 Associate Professor of Genetics, Afzalipour School of Medicine & Physiology Research Center, Kerman University of Medical Sciences, Kerman, Iran

3 Resident of Obstetrics & Genecology, Afzalipour School of Medicine, Kerman University of Medical Sciences, Kerman, Iran

4 Genetic Laboratory, Afzalipour Hospital, Kerman, Iran

Abstract
Background & Aims: Preeclampsia is one of the complications of pregnancy and a major cause of maternal mortality. Since, hypercoagulation is one of the risk factors, defined polymorphisms of V and II coagulation factors (G1691A and G20210A) may increase the risk of the disease.

Methods: This investigation was performed on blood samples of 64 preeclamptic women and control group. DNA of white blood cells were extracted using salt satutation method. Then, G1691A and G20210A polymorphisms were investigated using ARMS-PCR technique.

Results: Significant difference was found between the mean age of case (28.734 yrs) and control (24.921 yrs) groups (P=0.000196). But, mean of gestational age did not show significant difference between the case and control groups (34.719 wks & 34.421 wks respectively).  
Among the preeclamptic patients, we found two heterozygotes (3.1%) for each factor II and factor V. No homozygote mutation (0%) was found in this study, while we found one heterozygote subject (1.6%) for factor V in the control group.

Conclusion: in comparison of preeclamptic and control group for single nucleotid polymorphisms (G1691A and G20210A), no significant difference was found. Therefore, these polymorphisms cannot be considered as prediagnostic risk factors for preeclampsy. We suggest more wide genetic and invironmental investigations for finding preeclampsia risk factors.

Keywords

preeclampsia
Factor V Leiden
Prothrombin
  1. Cunningham FG, Leveno KJ, Bloom SL, Hauth JC, Rouse DJ, Spong CY. Williams obstetrics. 23rd ed. New York, McGraw-Hill, 2010; PP 756-85.
  2. Cunningham FG, Leveno KJ, Bloom SL, Hauth JC, Hauth LC, et al. Hypertensive disorders in pregnancy, In: Rouse D, Rainey B, Spong C, Wendel GD. (editors), Williams Obsterics.23rd ed., USA, McGraw-Hill companies, 2010; PP 706-757.
  3. Scott JR, Gibbs RS, Karlan BY, Haney AF. Danforth's obstetrics and gynecology. 9th ed., New York, Lippincott Williams & Wilkins, 2003;PP 143-153.
  4. Cunningham G, Gilstrap LC, Leveno KJ, Bloom L. Williams Obstetrics 2nd ed., Philadelphia, McGraw-Hill, 2004; PP 761-808.
  5. Roberts JM, Taylor RN, Musci TJ, Rodgers GM, Hubel CA, McLaughlin MK. Preeclampsia: an endothelial cell disorder. Am J Obstet Gynecol 1989; 161(5): 1200-4.
  6. Piazze J, Gioia S, Maranghi L, Anceschi M. Mean platelet and red blood cell volume measurements to estimate the severity of hypertension in pregnancy. J Perinat Med. 2006; 34(3): 246-7.
  7. Ceyhan T, Beyan C, Başer I, Kaptan K, Güngör S, Ifran A. The effect of pre-eclampsia on complete blood count, platelet count and mean platelet volume. Ann Hematol 2006; 85(5): 320-2.
  8. Missfelder-Lobos H, Teran E, Lees C, Albaiges G, Nicolaides KH. Platelet changes and subsequent development of pre-eclampsia and fetal growth restriction in women with abnormal uterine artery Doppler screening. Ultrasound Obstet Gynecol 2002; 19(5): 443-8.
  9. Lin J, August P. Genetic thrombophilias and pre-eclampsia: a metaanalysis. Obstet Gynecol 2005; 105(1): 182-92.
  10. Kosmas IP, Tatsioni A, Ioannidis JP. Association of Leiden mutation in factor V gene with hypertension in pregnancy and pre-eclampsia: ameta-analysis. J Hypertens 2003; 21(7): 1221-8.
  11. Donna S. D, Lesa M. N, Katrina E, Kenneth W. The factor V Leiden mutation may predispose women to severe preeclampsia. Am J Obstet Gynecol 1996; 175: 192-195.
  12. Dekker GA, de Vries JI, Doelitzsch PM, Huijgens PC, vonBlomberg BM, Jakobs C, et al. Underlying disorders associated with severe early-onset preeclampsia. Am J Obstet Gynecol 1995; 173(4): 1042-8.
  13. Dizon-Townson DS, Nelson LM, Easton K, Ward K. The factor VLeiden mutation may predispose women to severe preeclampsia. Am J Obstet Gynecol 1996; 175(4pt1): 902-5.
  14. Lindoff C, Ingemarsson I, Martinsson G, Segelmark M, Thysell H, Astedt B. Preeclampsia is associated with reduced response toactivated protein C. Am J Obstet Gynecol 1997; 176(2):457-60.
  15. Van Pampus MG, Dekker GA, Wolf H, Huijgens PC, KoopmanMM, von Blomberg BM, et al. High prevalence of hemostatic abnormalities in women with a history of preeclampsia. Am JObstet Gynecol 1999; 180(5): 1146-50.
  16. Bertina RM, Koeleman BP, Koster T, Rosendaal FR, Dirven RJ, et al. Mutation in blood coagulation factor V associated with resistance to activated protein C. Nature 1994; 369 (6475): 64-7.
  17. Dahlback B, Carlsson M, Svensson PJ. Familial thrombophilia due to a previously unrecognized mechanism characterized by poor anticoagulant response to activated protein C: prediction of a cofactor to activated protein C. Proc Natl Acad Sci 1993; 90(3): 1004-8.
  18. Grandone E, Margaglione M, Colaizzo D, Cappucci G, Scianname` N, et al. Prothrombotic genetic risk factors and the occurrence of gestational hypertension with or with outproteinuria. Thromb Haemost 1999; 81(3): 349-52.
  19. Kupferminc MJ, Fait G, Many A, Gordon D, Eldor A, Lessing JB. Severe preeclampsia and high frequency of genetic thrombophilic mutations. Obstet Gynecol 2000; 96: 45-9.
  20. Tranquilli AL, Giannubilo SR, Dell'Uomo B, Grandone E. Adverse pregnancy outcomes are associated with multiple maternal thrombophilic factors. Eur J Obstet Gynecol Reprod Biol 2004; 117(2): 144-7.
  21. Martinelli I, Battaglioli T, De Stefano V, Tormene D, Valdrè L, et al. The risk of first venous thromboembolism during pregnancy and puerperium in double heterozygotes for factor V Leiden and prothrombin G20210A. J Thromb Haemost 2008; 6(3): 494-8.
  22. De Stefano V, Leone G. Resistance to activated protein C due to mutated factor V as a novel cause of inherited thrombophilia. Haematologica 199h; 80(4): 344-56.
  23. SNP linked to Gene F5". NCBI. Available at: http://www.ncbi.nlm.nih.gov/SNP/snp_ref.cgi.
  24. Makris M. Thrombophilia: grading the risk . Blood 2009; 113: 5038-5039.
  25. Ridker PM, Miletich JP, Hennekens CH, Buring JE. Ethnic distribution of factor V Leiden in 4047 men and women. Implications for venous thromboembolism screening. JAMA 1997; 277 (16): 1305-7.
  26. Gregg JP, Yamane AJ, Grody WW. Prevalence of the factor V-Leiden mutation in four distinct American ethnic populations. Am J Med Genet 1997; 73(3): 334-6.
  27. De Stefano V, Chiusolo P, Paciaroni K, Leone G. Epidemiology of factor V Leiden: clinical implications. Semin Thromb Hemost 1998; 24(4): 367-79.
  28. Dashti AA, Jadaon MM. Race differences in the prevalence of the factor V Leiden mutation in Kuwaiti nationals. Mol Biol Rep 2011; 38(6): 3623-8.
  29. Bagheri M, Rad IA. A Multiplex Allele Specific Polymerase Chain Reaction (MAS-PCR) for the Detection of Factor V Leiden and Prothrombin G20210A. Maedica (Buchar) 2011; 6(1): 3-9.
  30. Rahimi Z, Vaisi-Raygani A, Mozafari H, Kharrazi H, Rezaei M, et al. Prevalence of factor V Leiden (G1691A) and prothrombin (G20210A) among Kurdish population from Western Iran. J Thromb Thrombolysis 2008; 25(3): 280-3.
  31. Miller SA, Dykes DD, Polesky HF. A simple salting out procedure for extracting DNA from human nucleated cells. Nucleic Acids Res 1988; 16(3): 1215-16.
  32. Newton CR, Graham A, Heptinstall LE, Powell SJ, Summeres C, Kalsheker N, Smith JC, Markham AF. Analysis of any point mutation in DNA. The amplification refractory mutation system (ARMS). Nucleic Acids Res 1989; 17(7): 2503-16.
  33. Behjati R, Modarressi MH, Jeddi-Tehrani M, Dokoohaki P, Ghasemi J, Zarnani AH, et al. Thrombophilic mutations in Iranian patients with infertility and recurrent spontaneous abortion. Ann Hematol 2006; 85(4): 268-71.
  34. Bagheri M, Rad IA, Nanbakhsh F. Factor V Leiden G1691A and factor II G20210A point mutations and pregnancy in North-West of Iran. Arch Gynecol Obstet 2011; 284(5): 1311-5.
  35. Malek-Khosravi S, Rahimi Z, Rahimi Z, Jalilvand F, Parsian A. Thrombophilic mutations and susceptibility to preeclampsia in Western Iran. J Thromb Thrombolysis 2012; 33(1): 109-15.
  36. Karimi S, Yavarian M, Azinfar A, Rajaei M, Azizi Kootenaee M. Evaluation the frequency of factor V Leiden mutation in pregnant women with preeclampsia syndrome in an Iranian population. Iran J Reprod Med 2012; 10(1): 59-66.
  37. Mello G, Parretti E, Marozio L, Pizzi C, Lojacono A, Frusca T, et al. Thrombophilia is significantly associated with severe preeclampsia: results of a large-scale, case-controlled study. Hypertension 2005; 46(6): 1270-4.
  38. Giovanni L, Antonio AP, Danilo C, Stefano G, Therese D, Elisabetta RM, et al. Thrombophilias and pregnancy complications: a case-control study. Int J Biomed Sci 2007; 3(3): 168-75.
  39. Giovanni L1, Antonio AP, Danilo C, Stefano G, Therese D, Elisabetta RM, et al. Thrombophilias and pregnancy complications: a case-control study. BJOG 2003; 110: 327-328.

 

 

Article View 5,429
PDF Download 23,687

Home

Editorial Board

Guide for Authors

Submit Manuscript

Guide for Reviewers

Contact Us