Volume 14, Issue 5 (5-2016)                   IJRM 2016, 14(5): 329-334 | Back to browse issues page


XML Persian Abstract Print


Download citation:
BibTeX | RIS | EndNote | Medlars | ProCite | Reference Manager | RefWorks
Send citation to:

Arabkhazaeli N, Ghanaat K, Hashemi-Soteh M B. H1299R in coagulation Factor V and Glu429Ala in MTHFR genes in recurrent pregnancy loss in Sari, Mazandaran. IJRM 2016; 14 (5) :329-334
URL: http://ijrm.ir/article-1-748-en.html
1- Department of Genetic, Faculty of Science, Damghan Branch, Islamic Azad University, Damghan, Iran
2- Department of Clinical Biochemistry and Genetics, Faculty of Medicine, Mazandaran University of Medical Sciences, Sari, Iran
3- Department of Clinical Biochemistry and Genetics, Faculty of Medicine, Mazandaran University of Medical Sciences, Sari, Iran , Hashemisoteh@gmail.com
Abstract:   (3021 Views)
Background: Recurrent pregnancy loss (RPL) is caused by different factors, including genetics and thrombophilia. Beside Factor V Leiden, another nucleotide change in a factor V (FV) gene (A4070G; His1299Arg) has been identified linking to hereditary thrombophilia. Also, two proposed MTHFR polymorphisms, C677T and A1298C (Glu429A) are linked with RPL.
Objective: In this study, the effect of two factors, A4070G in FV and A1298C in MTHFR are evaluated in RPL patients from Mazandaran province, Iran.
Materials and methods: Sample population of 100 women with RPL and 100 controls with Mazandarani ethnics from northern Iran were consist. The factor V (A4070G) and MTHFR (A1298C) polymorphisms were genotyped by PCR-RFLP.
Results: Molecular study showed 5 women from patients and 9 women from control group were heterozygous AG for A4070G. Frequency of "A" allele in patient and control groups was 97.5% (0.975) and 95.5% (0.955) respectively, and "G" allele frequency was 2.5% (0.025) and 4.5% (0.045) respectively. No significant association (p≤0.05) between FV A4070G genotype and RPL with an OR=1.88, CI 95%=0.6-5.82, was observed (p=0.4). Also, for A1298C, all patients and control individuals were AA genotype. "A" allele frequency in patients and control was 100% and "C" allele frequency was zero. There was no significant difference for A1298C between groups.
Conclusion: Our finding showed that A4070G and A1298C polymorphisms cannot be considered as a cause of PRL in women from Mazandaran province, northern Iran.
Full-Text [PDF 220 kb]   (743 Downloads) |   |   Full-Text (HTML)  (485 Views)  
Type of Study: Original Article |

References
1. Vettriselvi V, Vijayalakshmi K, Paul SFD, Venkatachalam P. ACE and MTHFR gene polymorphisms in unexplained recurrent pregnancy loss. J Obstet Gynaecol Res 2008; 34: 301-306. [DOI:10.1111/j.1447-0756.2008.00792.x]
2. Carp H, Salomon O, Seidman D, Dardik R, Rosenberg N, Inbal A. Prevalence of genetic markers for thrombophilia in recurrent pregnancy loss. Hum Reprod (Oxf Engl) 2002; 17:1633-1637. [DOI:10.1093/humrep/17.6.1633]
3. Sarig G, Younis JS, Hoffman R, Lanir N, Blumenfeld Z, Brenner B. Thrombophilia is common in women with idiopathic pregnancy loss and is associated with late pregnancy wastage. Fertil Steril 2002; 77: 342-347. [DOI:10.1016/S0015-0282(01)02971-5]
4. Kovalevsky G, Gracia CR, Berlin JA. Evaluation of the association between hereditary thrombophilias and recurrent pregnancy loss: a meta-analysis. Arch Intern Med 2004; 164: 558-563. [DOI:10.1001/archinte.164.5.558]
5. Ford HB, Schust DJ. Recurrent pregnancy loss: etiology, diagnosis, and therapy. Rev Obstet Gynecol 2009; 2: 76-83.
6. Rosing J, Tans G, Govers-Riemslag JW, Zwaal RF, Hemker HC. The role of phospholipids and factor Va in the prothrombinase complex. J Biol Chem 1980; 255: 274-283.
7. Bertina RM, Reitsma PH, Rosendaal FR, Vandenbroucke JP. Resistance to activated protein C and factor V Leiden as risk factors for venous thrombosis. Thromb Haemost 1995; 74: 449-453.
8. Lunghi B, Iacoviello L, Gemmati D, Dilasio MG, Castoldi E, Pinotti M, et al. Detection of new polymorphic markers in the factor V gene: association with factor V levels in plasma. Thromb Haemost 1996; 75: 45-48.
9. Alhenc-Gelas M, Nicaud V, Gandrille S,Van Dreden P, Amiral J, Aubry ML, et al. The factor V gene A4070G mutation and the risk of venous thrombosis. Thromb Haemost 1999; 81: 193-197.
10. Castaman G, Lunghi B, Missiaglia E, Bernardi F, Rodeghiero F. Phenotypic homozygous activated protein C resistance associated with compound heterozygosity for Arg506Gln (factor V Leiden) and His1299Arg substitutions in factor V. Br J Haematol 1997; 99: 257-261. [DOI:10.1046/j.1365-2141.1997.3993213.x]
11. Jacques PF, Bostom AG, Williams RR, Ellison RC, Eckfeldt JH, Rosenberg IH, et al. Relation between folate status, a common mutation in methylenetetrahydrofolate reductase, and plasma homocysteine concentrations. Circulation 1996; 93: 7-9. [DOI:10.1161/01.CIR.93.1.7]
12. Frosst P, Blom HJ, Milos R, Goyette P, Sheppard CA, Matthews RG,et al. A candidate genetic risk factor for vascular disease: a common mutation in methylenetetrahydrofolate reductase. Nat Genet 1995; 10: 111-113. [DOI:10.1038/ng0595-111]
13. Li M, Lau EM, Woo J. Methylene tetra hydrofolate reductase polymorphism (MTHFR C677T) and bone mineral density in Chinese men and women. Bone 2004; 35: 1369-1374. [DOI:10.1016/j.bone.2004.09.008]
14. Zetterberg H. Methylene tetra hydro folate reductase and trans cobalamin genetic polymorphisms in human spontaneous abortion: biological and clinical implications. Reprod Biol Endocrinol 2004; 2: 7-14. [DOI:10.1186/1477-7827-2-7]
15. De Re V, Cannizzaro R, Canzonieri V, Cecchin E, Caggiari L, De Mattia E,et al. MTHFR polymorphisms in gastric cancer and in first-degree relatives of patients with gastric cancer. Tumor Biol 2010; 31: 23-32. [DOI:10.1007/s13277-009-0004-1]
16. Agodi A, Barchitta M, Cipresso R, Marzagalli R, La Rosa N, Caruso M,et al. Distribution of p53, GST, and MTHFR polymorphisms and risk of cervical intraepithelial lesions in sicily. Int J Gynecol Cancer 2010; 20: 141-146. [DOI:10.1111/IGC.0b013e3181c20842]
17. Nakata Y, Katsuya T, Takami S, Sato N, Fu Y, Ishikawa K, et al. Methylenetetrahydrofolate reductase gene polymorphism relation to blood pressure and cerebrovascular disease. Am J Hypertens 1998; 11: 1019-1023. [DOI:10.1016/S0895-7061(98)00046-6]
18. Nelen WL, Blom HJ, Steegers EA, den Heijer M, Eskes TK, et al. Hyperhomocysteinemia and recurrent early pregnancy loss: a meta-analysis. Fertil Steril 2000; 74: 1196-1199. [DOI:10.1016/S0015-0282(00)01595-8]
19. Doggen Carine JM, Visser Marieke CH de, Vos Hans L, Bertina RM, Cats VM, Rosendaal FR, et al. The HR2 haplotype of factor V Is not associated with the risk of myocardial infarction. Thromb Haemost 2000; 84: 815-818.
20. Wu X, Zeng Z, Chen B, Yu J, Xue L, Hao Y,et al. Association between polymorphisms in interleukin‐17A and interleukin‐17F genes and risks of gastric cancer. Int J Cancer 2010; 127: 86-92. [DOI:10.1002/ijc.25027]
21. Naomi Q. Hanson, Ömer Aras, Tsai MY.C677T and A1298C polymorphisms of the Methylene tetra hydro folate reductase Gene: Incidence and effect of combined genotypes on plasma fasting and post-methionine load homocysteine in vascular disease. Clin Chem 2001; 47: 661-666.
22. Preston F, Rosendaal F, Walker I, Briët E, Berntorp E, Conard J, et al. Increased fetal loss in women with heritable thrombophilia. Lancet 1996; 348: 913-916. [DOI:10.1016/S0140-6736(96)04125-6]
23. Rai R, Shlebak A, Cohen H, Backos M, Holmes Z, Marriott K, et al. Factor V Leiden and acquired activated protein C resistance among 1000 women with recurrent miscarriage. Hum Reprod 2001; 16: 961-965. [DOI:10.1093/humrep/16.5.961]
24. Nowak-Göttl U, Sonntag B, Junker R, Cirkel U, von Eckardstein A. Evaluation of lipoprotein (a) and genetic prothrombotic risk factors in patients with recurrent foetal loss. Thromb Haemost 2000; 83: 350-351.
25. Zammiti W, Mtiraoui N, Mercier E, Abboud N, Saidi S, Mahjoub T, et al. Association of factor V gene polymorphisms (Leiden; Cambridge; Hong Kong and HR2 haplotype) with recurrent idiopathic pregnancy loss in Tunisia. A case-control study. Thromb Haemost 2009; 95: 612-617.
26. 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: 230-236. [DOI:10.1111/j.1600-0897.2006.00419.x]
27. 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: 360-368. [DOI:10.1111/j.1600-0897.2006.00376.x]
28. Soltanpour MS, Soheili Z, Pourfathollah AA, Samiei Sh, Meshkani R, Kiani AA, et al. The A1298C mutation in methylenetetrahydrofolate reductase gene and its association with idiopathic venous thrombosis in an iranian population. Lab Med 2011; 42: 213-216. [DOI:10.1309/LM5LWXCHVZY9RFOM]
29. Neagoş D, CreŃu R, Sfetea RC, Mierla D, Bohiltea LC. Investigation of the relationship between the risk of spontaneous abortion and C677T and A1298C polymorphisms of the methylenetetrahydrofolate reductase gene. Revista Română de Medicină de Laborator 2012; 20: 335-343. (In Romanian)
30. Rodríguez-Guillén MdR, Torres-Sánchez L, Chen J, Galván-Portillo M, Blanco-Mu-oz J, Anaya MA, et al. Maternal MTHFR polymorphisms and risk of spontaneous abortion. Salud pública Méx 2009; 51: 19-25. [DOI:10.1590/S0036-36342009000100006]
31. Spiroski I, Kedev S, Antov S, Krstevska M, Dzhekova-Stojkova S, Bosilkova G, et al. Methylenetetrahydrofolate reductase (MTHFR-677 and MTHFR-1298) genotypes and haplotypes and plasma homocysteine levels in patients with occlusive artery disease and deep venous thrombosis. Acta Biochim Pol 2008; 55: 587- 594.
32. Freitas AI, Mendonça I, Guerra G, Brión M, Reis RP, Carracedo A, et al. Methylenetetrahydrofolate reductase gene, homocysteine and coronary artery disease: the A1298C polymorphism does matter. Inferences from a case study (Madeira, Portugal). Thromb Res 2008; 122: 648-656. [DOI:10.1016/j.thromres.2008.02.005]
33. Bakker R, Brandjes D. Hyperhomocysteinaemia and associated disease. Pharm World Sci 1997; 19: 126-132. [DOI:10.1023/A:1008634632501]
34. Wang X, Lin Q, Ma Z, Zhao AM. [C677T and A1298C mutation of the methylenetetrahydrofolate reductase gene in unexplained recurrent spontaneous abortion]. Zhonghua Fu Chan Ke Za Zhi 2004; 39: 238-241. (In Chinese)
35. Mtiraoui N, Zammiti W, Ghazouani L, Braham NJ, Saidi S, Finan RR, et al. Methylenetetrahydrofolate reductase C677T and A1298C polymorphism and changes in homocysteine concentrations in women with idiopathic recurrent pregnancy losses. Reproduction 2006; 131: 395-401. [DOI:10.1530/rep.1.00815]
36. Hohlagschwandtner M, Unfried G, Heinze G, Huber JC, Nagele F, Tempfer C. Combined thrombophilic polymorphisms in women with idiopathic recurrent miscarriage. Fertil Steril 2003; 79: 1141-1148. [DOI:10.1016/S0015-0282(02)04958-0]
37. Khaleghparast A, Morovvati S, Noormohammadi Z. Evaluation of the association between the C677T and A1298C polymorphisms of MTHFR gene and recurrent miscarriage. Sci J Iran Blood Transfus org 2011; 8: 88-95.
38. PoursadeghZonouzi A, Chaparzadeh N, Asghari Estiar M, Mehrzad Sadaghiani M, Farzadi L, Ghasemzadeh A, et al. Methylene tetra hydro folate reductase C677T and A1298Cmutations in women with recurrent spontaneous abortions in the northwest of Iran. ISRN Obstet Gynecol 2012; 2012: 1-6. [DOI:10.5402/2012/945486]

Send email to the article author


Rights and permissions
Creative Commons License This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.

Designed & Developed by : Yektaweb