Advanced Biomedical Research

Factor V Leiden does not have a role in cryptogenic ischemic stroke among Iranian young adults

Authors

1 Isfahan Neurosciences Research Center, Department of Neurology, Isfahan University of Medical Sciences, Isfahan, Iran

2 Department of Genetics, Isfahan University of Medical Sciences, Isfahan, Iran

Abstract

Background: Different risk factors have been suggested for ischemic stroke in young adults. In a group of these patients despite of extensive diagnostic work-up, the primary cause remains unknown. Coagulation tendency is accounted as a possible cause in these patients. Previous studies on factor V Leiden (FVL) as the main cause of inherited thrombophilia for clarifying the role of FVL in stroke have resulted in controversial findings. The current study investigates the role of this factor in ischemic stroke among Iranians.
Materials and Methods: This case-control study was performed between September 2007 and December 2008 in Isfahan, Iran. The case group comprised of 22 patients of which 15 were males and 7 were females with age range of ≤50 years, diagnosed as ischemic stroke without classic risk factors and the control group consisted of 54 healthy young adults. After filling consent form, venous blood samples were obtained and sent to the laboratory for genetic examination.
Results: No FVL mutation was found in the case group. There was one carrier of the mutation as heterozygous in the control group (relative frequency = 1.85%).
Conclusions: Based on our study, FVL might not be considered as an independent risk factor for ischemic stroke in Iranian individuals who are not suffering from other risk factors of ischemic stroke.

Keywords

1. Azarpazhooh MR, Etemadi MM, Donnan GA, Mokhber N, Majdi MR, Ghayour-Mobarhan M, et al. Excessive incidence of stroke in Iran: Evidence from the Mashhad Stroke Incidence Study (MSIS), a population-based study of stroke in the Middle East. Stroke 2010;41:e3-10.  Back to cited text no. 1
    
2. Varona JF, Guerra JM, Bermejo F, Molina JA, Gomez de la Cámara A. Causes of ischemic stroke in young adults, and evolution of the etiological diagnosis over the long term. Eur Neurol 2007;57:212-8.  Back to cited text no. 2
    
3. Jacobs BS, Boden-Albala B, Lin IF, Sacco RL. Stroke in the young in the northern Manhattan stroke study. Stroke 2002;33:2789-93.  Back to cited text no. 3
    
4. Kristensen B, Malm J, Carlberg B, Stegmayr B, Backman C, Fagerlund M, et al. Epidemiology and etiology of ischemic stroke in young adults aged 18 to 44 years in northern Sweden. Stroke 1997;28:1702-9.  Back to cited text no. 4
    
5. Ahangar AA, Ashraf Vaghefi SB, Ramaezani M. Epidemiological evaluation of stroke in Babol, northern Iran (2001-2003). Eur Neurol 2005;54:93-7.  Back to cited text no. 5
    
6. Leys D, Bandu L, Hénon H, Lucas C, Mounier-Vehier F, Rondepierre P, et al. Clinical outcome in 287 consecutive young adults (15 to 45 years) with ischemic stroke. Neurology 2002;59:26-33.  Back to cited text no. 6
    
7. Jamieson DG. Diagnosis of ischemic stroke. Am J Med 2009;122:S14-20.  Back to cited text no. 7
    
8. Karttunen V, Alfthan G, Hiltunen L, Rasi V, Kervinen K, Kesäniemi YA, et al. Risk factors for cryptogenic ischaemic stroke. Eur J Neurol 2002;9:625-32.  Back to cited text no. 8
    
9. Kim RJ, Becker RC. Association between factor V Leiden, prothrombin G20210A, and methylenetetrahydrofolate reductase C677T mutations and events of the arterial circulatory system: A meta-analysis of published studies. Am Heart J 2003;146:948-57.  Back to cited text no. 9
    
10. Urbanus RT, Siegerink B, Roest M, Rosendaal FR, de Groot PG, Algra A. Antiphospholipid antibodies and risk of myocardial infarction and ischaemic stroke in young women in the RATIO study: A case-control study. Lancet Neurol 2009;8:998-1005.  Back to cited text no. 10
    
11. Longstreth WT Jr, Rosendaal FR, Siscovick DS, Vos HL, Schwartz SM, Psaty BM, et al. Risk of stroke in young women and two prothrombotic mutations: Factor V Leiden and prothrombin gene variant (G20210A) Stroke 1998;29:577-80.  Back to cited text no. 11
    
12. Margaglione M, D'Andrea G, Giuliani N, Brancaccio V, De Lucia D, Grandone E, et al. Inherited prothrombotic conditions and premature ischemic stroke: Sex difference in the association with factor V Leiden. Arterioscler Thromb Vasc Biol 1999;19:1751-6.  Back to cited text no. 12
    
13. Voetsch B, Damasceno BP, Camargo EC, Massaro A, Bacheschi LA, Scaff M, et al. Inherited thrombophilia as a risk factor for the development of ischemic stroke in young adults. Thromb Haemost 2000;83:229-33.  Back to cited text no. 13
    
14. de Paula Sabino A, Ribeiro DD, Carvalho Md, Cardoso J, Dusse LM, Fernandes AP. Factor V Leiden and increased risk for arterial thrombotic disease in young Brazilian patients. Blood Coagul Fibrinolysis 2006;17:271-5.  Back to cited text no. 14
    
15. Blinkenberg EØ, Kristoffersen AH, Sandberg S, Steen VM, Houge G. Usefulness of factor V Leiden mutation testing in clinical practice. Eur J Hum Genet 2010;18:862-6.  Back to cited text no. 15
    
16. Szolnoki Z, Somogyvári F, Szabó M, Fodor L. A clustering of unfavourable common genetic mutations in stroke cases. Acta Neurol Scand 2000;102:124-8.  Back to cited text no. 16
    
17. Nabavi DG, Junker R, Wolff E, Lüdemann P, Doherty C, Evers S, et al. Prevalence of factor V Leiden mutation in young adults with cerebral ischaemia: A case-control study on 225 patients. J Neurol 1998;245:653-8.  Back to cited text no. 17
    
18. Lalouschek W, Aull S, Serles W, Schnider P, Mannhalter C, Pabinger-Fasching I, et al. C677T MTHFR mutation and factor V Leiden mutation in patients with TIA/minor stroke: A case-control study. Thromb Res 1999;93:61-9.  Back to cited text no. 18
    
19. Huisman MV, Rosendaal F. Thrombophilia. Curr Opin Hematol 1999;6:291-7.  Back to cited text no. 19
    
20. Adams HP Jr, Bendixen BH, Kappelle LJ, Biller J, Love BB, Gordon DL, et al. Classification of subtype of acute ischemic stroke. Definitions for use in a multicenter clinical trial. TOAST. Trial of Org 10172 in Acute Stroke Treatment. Stroke 1993;24:35-41.  Back to cited text no. 20
    
21. Bertina RM, Koeleman BP, Koster T, Rosendaal FR, Dirven RJ, de Ronde H, et al. Mutation in blood coagulation factor V associated with resistance to activated protein C. Nature 1994;369:64-7.  Back to cited text no. 21
    
22. Hamedani AG, Cole JW, Mitchell BD, Kittner SJ. Meta-analysis of factor V Leiden and ischemic stroke in young adults: The importance of case ascertainment. Stroke 2010;41:1599-603.  Back to cited text no. 22
    
23. Marjot T, Yadav S, Hasan N, Bentley P, Sharma P. Genes associated with adult cerebral venous thrombosis. Stroke 2011;42:913-8.  Back to cited text no. 23
    
24. Juul K, Tybjaerg-Hansen A, Steffensen R, Kofoed S, Jensen G, Nordestgaard BG. Factor V Leiden: The Copenhagen City Heart Study and 2 meta-analyses. Blood 2002;100:3-10.  Back to cited text no. 24
    
25. Lucotte G, Mercier G. Population genetics of factor V Leiden in Europe. Blood Cells Mol Dis 2001;27:362-7.  Back to cited text no. 25
    
26. Bauduer F, Lacombe D. Factor V Leiden, prothrombin 20210A, methylenetetrahydrofolate reductase 677T, and population genetics. Mol Genet Metab 2005;86:91-9.  Back to cited text no. 26
    
27. Irani-Hakime N, Tamim H, Kreidy R, Almawi WY. The prevalence of factor V R506Q mutation-Leiden among apparently healthy Lebanese. Am J Hematol 2000;65:45-9.  Back to cited text no. 27
    
28. Hussein AS. High prevalence of three prothrombotic polymorphisms among Palestinians: Factor V G1691A, factor II G20210A and methylenetetrahydrofolate reductase C677T. J Thromb Thrombolysis 2012;34:383-7.  Back to cited text no. 28
    
29. Kupeli E, Verdi H, Simsek A, Atac FB, Eyuboglu FO. Genetic mutations in Turkish population with pulmonary embolism and deep venous thrombosis. Clin Appl Thromb Hemost 2011;17:E87-94.  Back to cited text no. 29
    
30. Akar N, Akar E, Yilmaz E. Coexistence of factor V 1691 G-A and factor V 4070 A-G mutation in turkish thromboembolic patients. Am J Hematol 2000;65:88.  Back to cited text no. 30
    
31. Al-Allawi NA, Jubrael JM, Hilmi FA. Factor V Leiden in blood donors in Baghdad (Iraq). Clin Chem 2004;50:677-8.  Back to cited text no. 31
    
32. Nasiruddin, Zahur-ur-Rehman, Anwar M, Ahmed S, Ayyub M, Ali W. Frequency of factor V leiden mutation. J Coll Physicians Surg Pak 2005;15:15-7.  Back to cited text no. 32
    
33. Shi C, Kang X, Wang Y, Zhou Y. The coagulation factor V Leiden, MTHFRC677T variant and eNOS 4ab polymorphism in young Chinese population with ischemic stroke. Clin Chim Acta 2008;396:7-9.  Back to cited text no. 33
    
34. Jun ZJ, Ping T, Lei Y, Li L, Ming SY, Jing W. Prevalence of factor V Leiden and prothrombin G20210A mutations in Chinese patients with deep venous thrombosis and pulmonary embolism. Clin Lab Haematol 2006;28:111-6.  Back to cited text no. 34
    
35. Angchaisuksiri P, Pingsuthiwong S, Aryuchai K, Busabaratana M, Sura T, Atichartakarn V, et al. Prevalence of the G1691A mutation in the factor V gene (factor V Leiden) and the G20210A prothrombin gene mutation in the Thai population. Am J Hematol 2000;65:119-22.  Back to cited text no. 35
    
36. Rahimi Z, Mozafari H, Shahriari-Ahmadi A, Alimogaddam K, Ghavamzadeh A, Aznab M, et al. Deep venous thrombosis and thrombophilic mutations in western Iran: Association with factor V Leiden. Blood Coagul Fibrinolysis 2010;21:385-8.  Back to cited text no. 36
    
37. Rahimi Z, Vaisi-Raygani A, Mozafari H, Kharrazi H, Rezaei M, Nagel RL. Prevalence of factor V Leiden (G1691A) and prothrombin (G20210A) among Kurdish population from Western Iran. J Thromb Thrombolysis 2008;25:280-3.  Back to cited text no. 37
    
38. Zeinali S, Duca F, Zarbakhsh B, Tagliabue L, Mannucci PM. Thrombophilic mutations in Iran. Thromb Haemost 2000;83:351-2.  Back to cited text no. 38
    
39. 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;85:268-71.  Back to cited text no. 39
    
40. 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;6:3-9.  Back to cited text no. 40
Advanced Biomedical Research
Volume 2014, February
February 2014
Pages 1-5