Skip to main content
Log in

Prevalence of the prothrombin G20210A polymorphism in the Lebanese population: use of a reverse hybridization strip assay approach

  • Published:
Molecular Biology Reports Aims and scope Submit manuscript

Abstract

The factor II (prothrombin) G20210A gene polymorphism is the second most common SNP reported in VTE where it is associated with elevated plasma prothrombin levels and with a 3-fold increased risk. We studied the distribution of the G/G, G/A, and A/A genotypes of the Prothrombin G20210A gene mutation in the general Lebanese population using a novel technique in order to assess their prevalence, compare the results to previously reported data and to describe an available method that will permit easy and fast identification of the mutation. Prothrombin different genotypes were determined using the Cardiovascular Disease (CVD) StripAssay which is based on a Polymerase Chain Reaction-Reverse hybridization technique and DNA from 205 unrelated healthy donors from our HLA-bank was used. The prevalence of G/G, G/A, and A/A genotypes was found to be 98.54, 1.46, and 0%, respectively, with G and A allelic frequency of 99 and 1%, respectively. The sampled Lebanese population showed prothrombin genotypes distribution similar to Caucasians, and our results are comparable to other reports on the Lebanese healthy individuals. However, this is the first report on the prevalence of prothrombin G20210A mutation using this technique. Our results suggest that this approach is reliable and can be used as an assessment for thrombophilia profile. In addition, future investigations should be conducted to assess the contribution of the prothrombin G20210A mutation, on its own and in collaboration with other factors, in various clinical entities notably VTE.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Rosendaal FR (1999) Venous thrombosis: a multicausal disease. Lancet 353:1167–1173

    Article  PubMed  CAS  Google Scholar 

  2. Bertina RM, Koeleman BPC, Koster T, Rosendaal FR, Dirven RJ, de Ronde H, van der Velden PA, Reitsma PH (1994) Mutation in blood coagulation factor V associated with resistance to activated protein C. Nature 369:64–67

    Article  PubMed  CAS  Google Scholar 

  3. Royle NJ, Irwin DM, Koschinsky ML, MacGillivray RTA, Hamerton JL (1987) Human genes encoding prothrombin and ceruloplasmin map to 11p11–q12 and 3q21–24, respectively. Somat Cell Mol Genet 13:285

    Article  PubMed  CAS  Google Scholar 

  4. 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 88:3698–3703

    PubMed  CAS  Google Scholar 

  5. Kirschbaum NE, Foster PA (1995) The polymerase chain reaction with sequence specific primers for the detection of the factor V mutation associated with activated protein C resistance. Thromb Haemost 74:874–878

    PubMed  CAS  Google Scholar 

  6. Hezard N, Cornillet-Lefebvre P, Gillot L, Potron G, Nguyen P (1998) Multiplex ASA PCR for a simultaneous determination of factor V Leiden gene, G–A 20210 prothrombin gene and C–T 677 MTHFR gene mutations. Thromb Haemost 79:1054–1055

    PubMed  CAS  Google Scholar 

  7. Saiki RK, Chang CA, Levenson CH, Warren TC, Boehm CD, Kazazian HH Jr, Erlich HA (1988) Diagnosis of sickle cell anemia and beta-thalassemia with enzymatically amplified DNA and nonradioactive allele-specific oligonucleotide probes. N Engl J Med 319:537–541

    Article  PubMed  CAS  Google Scholar 

  8. Nauck M, Marz M, Weiland H (2000) Evaluation of the Roche diagnostics LightCycler-Factor V Leiden mutation detection kit and the LightCycler-Prothrombin mutation detection kit. Clin Biochem 33:213–216

    Article  PubMed  CAS  Google Scholar 

  9. von Ahsen N, Schutz E, Armstrong VW, Oellerich M (1999) Rapid detection of prothrombotic mutations of prothrombin (G20210A), factor V (G1691A), and methylenetetrahydrofolate Reductase (C677T) by real-time fluorescence PCR with the LightCycler. Clin Chem 45:694–696

    Google Scholar 

  10. Lay MJ, Wittwer CT (1997) Real-time fluorescence genotyping of factor V Leiden during rapid-cycle PCR. Clin Chem 43:2262–2267

    PubMed  CAS  Google Scholar 

  11. Rosendaal FR, Doggen CJM, Zivelin A, Arruda VR, Aiach M, Siscovick DS, Hillarp A, Watzke HH, Bernardi F, Cumming AM, Preston FE, Reitsma PH (1998) Geographic distribution of the 20210 G to A prothrombin variant. Thromb Haemost 79:700

    Google Scholar 

  12. Brown K, Luddington R, Williamson D, Baker P, Baglin T (1997) Risk of venous thromboembolism associated with a G to A transition at position 20210 in the 38-untranslated region of the prothrombin gene. Br J Haematol 98:907

    Article  PubMed  CAS  Google Scholar 

  13. Cumming AM, Keeney S, Salden A, Bhavnani M, Shwe KH, Hay CRM (1997) The prothrombin gene G20210A variant: prevalence in a UK anticoagulant clinic population. Br J Haematol 98:353

    Article  PubMed  CAS  Google Scholar 

  14. Hillarp A, Zoller B, Svensson PJ, Dahlback B (1997) The 20210 A allele of the prothrombin gene is a common risk factor among Swedish outpatients with verified deep vein thrombosis. Thromb Haemost 78:990

    PubMed  CAS  Google Scholar 

  15. Vargas M, Soto I, Pinto CR, Urgelles MF, Batalla A, Rodriguez-Reguero J, Cortina A, Alvarez V, Coto E (1999) The prothrombin 20210A allele and the factor V Leiden are associated with venous thrombosis but not with early coronary artery disease. Blood Coagul Fibrinolysis 10:39–41

    Article  PubMed  CAS  Google Scholar 

  16. Cattaneo M, Chantarangkul V, Taioli E, Santos JH, Tagliabue L (1999) The G20210A mutation of the prothrombin gene in patients with previous first episodes of deep-vein thrombosis: prevalence and association with factor V G1691A, methylenetetrahydrofolate reductase C677T and plasma prothrombin levels. Thromb Res 93:1–8

    Article  PubMed  CAS  Google Scholar 

  17. Antoniadi T, Hatzis T, Kroupis C, Economou-Petersen E, Petersen MB (1999) Prevalence of factor V Leiden, prothrombin G20210A, and MTHFR C677T mutations in a Greek population of blood donors. Am J Hematol 61:265–267

    Article  PubMed  CAS  Google Scholar 

  18. Keenan C, Livingstone WJ, White B, Mynett-Johnson L, Cusack S, Lawler M, Smith OP (2000) Prevalence of the prothrombin G20210A mutation in the Irish populations: use of a novel polymerase chain reaction approach. Blood Coagul Fibrinolysis 11:669–672

    Article  PubMed  CAS  Google Scholar 

  19. Renner W, Koppel H, Hoffmann C, Schallmoser K, Stanger O, Toplak H, Wascher TC, Pilger E (2000) Prothrombin G20210A, factor V Leiden, and factor XIII Val34Leu: common mutations of blood coagulation factors and deep vein thrombosis in Austria. Thromb Res 99:35–39

    Article  PubMed  CAS  Google Scholar 

  20. Coen D, Zadro R, Honović L, Banfić L, Stavljenić Rukavina A (2001) Prevalence and association of the factor V Leiden and prothrombin G20210A in healthy subjects and patients with venous thromboembolism. Croat Med J 42:488–492

    PubMed  CAS  Google Scholar 

  21. Dilley A, Hooper WC, Austin H, Lally C, Wenger NK, Evatt BL (1997) The prevalence of the prothrombin 20210 G=A variant in African Americans. Blood 90:652a

    Google Scholar 

  22. Franco RF, Elion J, Tavella MH, Araujo AG, Zago MA (1997) Heterogeneous distribution of the 20210G=A prothrombin and 677C=T methylenetetrahydrofolate reductase mutations in different human populations: relevance for vascular disease risk. Blood 90:3130a

    Google Scholar 

  23. Isshiki I, Murata M, Watanabe R, Matsubara Y, Kawano K, Aoki N, Yoshino H, Ishikawa K, Watanabe G, Ikeda Y (1998) Frequencies of prothrombin 20210 G=A mutation may be different among races studies on Japanese populations with various forms of thrombotic disorders and healthy subjects. Blood Coagul Fibrinol 9:105

    Article  CAS  Google Scholar 

  24. Hessner MJ, Luhm RA, Pearson SL, Endean DJ, Friedman KD, Montgomery RR (1999) Prevalence of prothrombin G20210A, factor V G1691A (Leiden), and methylenetetrahydrofolate reductase (MTHFR) C677T in seven different populations determined by multiplex allele-specific PCR. Thromb Haemost 81:733–738

    PubMed  CAS  Google Scholar 

  25. Bertina RM (1998) The prothrombin 20210 G to A variation and thrombosis. Curr Opin Hematol 5:339–342

    Article  PubMed  CAS  Google Scholar 

  26. Franco RF, Santos SE, Elion J, Tavella MH, Zago MA (1998) Prevalence of the G20210A polymorphism in the 3′-untranslated region of the prothrombin gene in different human populations. Acta Haematol 100:9–12

    Article  PubMed  CAS  Google Scholar 

  27. Bick RL (2003) Prothrombin G20210A mutation, antithrombin, heparin cofactor II, protein C, and protein S defects. Hematol Oncol Clin North Am 17:9–36

    Article  PubMed  Google Scholar 

  28. Ameen G, Irani-Hakime N, Fawaz NA, Mahjoub T, Almawi WY (2005) An Arab selective gradient in the distribution of factor V G1691A (Leiden), prothrombin G20210A, and methylenetetrahydrofolate reductase (MTHFR) C677T. J Thromb Haemost 3:2126–2127

    Article  PubMed  CAS  Google Scholar 

  29. Almawi WY, Keleshian SH, Borgi L, Fawaz NA, Abboud N, Mtiraoui N, Mahjoub T (2005) Varied prevalence of factor V G1691A (Leiden) and prothrombin G20210A single nucleotide polymorphisms among Arabs. J Thromb Thrombolysis 20:163–168

    Article  PubMed  CAS  Google Scholar 

  30. Tamim H, Finan RR, Almawi WY (2002) Prevalence of two thrombophilia predisposing mutations: factor V G1691A (R506Q; Leiden) and prothrombin G20210A, among healthy Lebanese. Thromb Haemost 88:691–692

    PubMed  Google Scholar 

  31. Taher A, Khalil I, Abou-Merhi R, Shamseddine A, Bazarbachi A (2003) High prevalence of prothrombin G20210A mutation among patients with deep venous thrombosis in Lebanon. Thromb Haemost 89:945–946

    PubMed  CAS  Google Scholar 

  32. Girolami A, Simioni P, Scarano L, Carraro G (1999) Prothrombin and the prothrombin 20210 G to A polymorphism: their relationship with hypercoagulability and thrombosis. Blood Rev 13:205–210

    Article  PubMed  CAS  Google Scholar 

  33. Ayyildiz O, Kalkanli S, Batun S, Aybak M, Isikdogan A, Tiftik N, Bolaman Z, Soker M, Muftuoglu E (2004) Prothrombin G20210A gene mutation with LightCycler polymerase chain reaction in venous thrombosis and healthy population in the southeast of Turkey. Heart Vessels 19:164–166

    Article  PubMed  Google Scholar 

  34. Torres JD, Cardona H, Alvarez L, Cardona-Maya W, Castañeda SA, Quintero-Rivera F, Cadavid A, Bedoya G, Tobón L (2006) Inherited thrombophilia is associated with deep vein thrombosis in a Colombian population. Am J Hematol 81:933–937

    Article  PubMed  CAS  Google Scholar 

  35. Miyata T, Kawasaki T, Fujimura H, Uchida K, Tsushima M, Kato H (1998) The prothrombin gene G20210A mutation is not found among Japanese patients with deep vein thrombosis and healthy individuals. Blood Coagul Fibrinolysis 9:451–452

    Article  PubMed  CAS  Google Scholar 

  36. Kim TW, Kim WK, Lee JH, Kim SB, Kim SW, Suh C, Lee KH, Lee JS, Seo EJ, Chi HS, Kim SH (1998) Low prevalence of activated protein C resistance and coagulation factor V Arg506 to Gln mutation among Korean patients with deep vein thrombosis. J Korean Med Sci 13:587–590

    PubMed  CAS  Google Scholar 

  37. Angchaisuksiri P, Pingsuthiwong S, Aryuchai K, Busabaratana M, Sura T, Atichartakarn V, Sritara P (2000) 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 65:119–122

    Article  PubMed  CAS  Google Scholar 

  38. Zivelin A, Rosenberg N, Faier S, Kornbrot N, Peretz H, Mannhalter C, Horellou MH, Seligsohn U (1998) A single genetic origin for the common prothrombotic G20210A polymorphism in the prothrombin gene. Blood 92:1119–1124

    PubMed  CAS  Google Scholar 

  39. Burzotta F, Paciaroni K, De Stefano V, Chiusolo P, Manzoli A, Casorelli I, Leone AM, Rossi E, Leone G, Maseri A, Andreotti F (2002) Increased prevalence of the G20210A prothrombin gene variant in acute coronary syndromes without metabolic or acquired risk factors or with limited extent of disease. Eur Heart J 23:26–30

    Article  PubMed  CAS  Google Scholar 

  40. Rees DC, Chapman NH, Webster MT, Guerreiro JF, Rochette J, Clegg JB (1999) Born to clot: the European burden. Br J Haematol 105:564–566

    Article  PubMed  CAS  Google Scholar 

  41. Hillarp A, Zöller B, Svensson PJ, Dahlbäck B (1997) The 20210 A allele of the prothrombin gene is a common risk factor among Swedish outpatients with verified deep venous thrombosis. Thromb Haemost 78:990–992

    PubMed  CAS  Google Scholar 

  42. Bouaziz-Borgi L, Almawi WY, Mtiraoui N, Nsiri B, Keleshian SH, Kreidy R, Louzir B, Hezard N, Mahjoub T (2006) Distinct association of factor V-Leiden and prothrombin G20210A mutations with deep venous thrombosis in Tunisia and Lebanon. Am J Hematol 81:641–643

    Article  PubMed  CAS  Google Scholar 

  43. Angeline T, Bentley HA, Hawk AB, Manners RJ, Mokashi HA, Jeyaraj N, Tsongalis GJ (2005) Prevalence of the Factor V G1691A and the Factor II/prothrombin G20210A gene polymorphisms among Tamilians. Exp Mol Pathol 79:9–13

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Rami A. R. Mahfouz.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Sabbagh, A.S., Ibrahim, G., Kanaan, Z. et al. Prevalence of the prothrombin G20210A polymorphism in the Lebanese population: use of a reverse hybridization strip assay approach. Mol Biol Rep 36, 399–403 (2009). https://doi.org/10.1007/s11033-007-9193-0

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11033-007-9193-0

Keywords

Navigation