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Thromb Haemost 1999; 81(05): 733-738
DOI: 10.1055/s-0037-1614563
Rapid Communication
Schattauer GmbH

Prevalence of Prothrombin G20210A, Factor V G1691A (Leiden), and Methylenetetrahydrofolate Reductase (MTHFR) C677T in Seven Different Populations Determined by Multiplex Allele-specific PCR

Martin J. Hessner
1   From the Diagnostic Laboratories of the Blood Center, Milwaukee, USA
,
Robert A. Luhm
1   From the Diagnostic Laboratories of the Blood Center, Milwaukee, USA
,
Steven L. Pearson
1   From the Diagnostic Laboratories of the Blood Center, Milwaukee, USA
,
Debra J. Endean
1   From the Diagnostic Laboratories of the Blood Center, Milwaukee, USA
,
Kenneth D. Friedman
1   From the Diagnostic Laboratories of the Blood Center, Milwaukee, USA
,
Robert R. Montgomery
1   From the Diagnostic Laboratories of the Blood Center, Milwaukee, USA
› Author Affiliations
Further Information

Publication History

Received 30 June 1998

Accepted after resubmission 27 January 1999

Publication Date:
09 December 2017 (online)

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Summary

Individuals belonging to six racial groups (African American, Asian Indian, Caucasian, Hispanic, Korean, Native American), and a seventh group comprised of referred patients with thrombosis were genotyped for the prothrombin G20210A mutation, the factor V G1691A (Leiden) mutation, and the methylenetetrahydrofolate reductase (MTHFR) C677T mutation by multiplexed allele-specific PCR. The prothrombin 20210A and factor V 1691A allele frequencies in the thrombosis patients, 3.2% and 9.5%, were significantly higher than those in the random Caucasians, 1.3% and 1.8%, (p = 0.043 and p <0.001, respectively). The relative risk of venous thrombosis was determined to be 2.4-fold for carriers of the prothrombin 20210A allele (odds ratio = 2.54; 95% confidence interval = 0.94, 6.82) and 4.5-fold for carriers of the factor V 1691A allele (odds ratio = 5.06; 95% confidence interval = 2.25, 11.36). Among the seven populations, significant differences were observed in the MTHFR 677T allele distribution, however this mutation was not determined to be a risk factor for venous thrombosis in the patient group studied, either alone or in combination with the pro-thrombin 20210A and/or the factor V 1691A allele(s).

 

  • References

  • 1 Kierkegaard A. Incidence of acute deep vein thrombosis in two districts. A phlebographic study. Chir Scand 1981; 246:: 267-9.
    PubMedGoogle Scholar
  • 2 Koeleman BPC, Reitsma PH, Allaart CF, Bertina RM. Activated protein C resistance as an additional risk factor for thrombosis in protein C deficient families.. Blood 1994; 84: 1031-5.
    PubMedGoogle Scholar
  • 3 Zoller B, Berntsdotte A, Garcia de Frutos P, Dahlbäck B. Resistance to activated protein C as an additional risk factor in hereditary deficiency of protein S.. Blood 1995; 85: 3518-23.
    PubMedGoogle Scholar
  • 4 Cattaneo M, Tsai MY, Bucciarelli P, Taioli E, Zighetti ML, Bignell M, Mannucci PM. A common mutation in the methylenetetrahydrofolate reductase gene (C677T) increase risk for deep-vein thrombosis in patients with mutant factor V (factor V:Q 506 ).. Arterioscler Thromb Vasc Biol 1997; 17: 1662-6.
    CrossrefPubMedGoogle Scholar
  • 5 Bertina RM, van Tilburg NH, de Fouw NJ, Haverkate F. Thrombin, a link between coagulation activation and fibrinolysis.. Ann N Y Acad Sci 1992; 667: 239-48.
    CrossrefPubMedGoogle Scholar
  • 6 Dang OD, Vindigni A, di Cera E. An allosteric switch controls the procoagulant and anticoagulant activities of thrombin.. Proc Natl Acad Sci USA 1995; 92: 5977-81.
    CrossrefPubMedGoogle Scholar
  • 7 Poort SR, Rosendaal FR, Reitsma PH, Bertina RM. 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 1996; 88: 3698-703.
    PubMedGoogle Scholar
  • 8 Cumming AM, Keeney S, Salden A, Bhavnani M, Shwe KH, Hay CRM. The prothrombin G20210A variant: prevalence in a U.K. anticoagulant clinic population.. The Br J Haematol 1997; 98: 353-5.
    PubMedGoogle Scholar
  • 9 Hillarp A, Zoller B, Svensson PJ, Dahlbäck B. The 20210 A allele of the prothrombin gene is a common risk factor among Swedish outpatients with verified deep venous thrombosis.. Thromb Haemost 1997; 78: 990-2.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 10 Dahlbäck B, Carlson M, Svensson PJ. Familial thrombophilia due to a previously unrecognized mechanism characterized by a poor anticoagulant response to activated protein C: prediction of a cofactor to activated protein C.. Proc Natl Acad Sci USA 1993; 90: 1004-8.
    CrossrefPubMedGoogle Scholar
  • 11 Svensson PJ, Dahlbäck B. Resistance to activated protein C as a basis for venous thrombosis.. New Engl J Med 1994; 330: 517-21.
    CrossrefPubMedGoogle Scholar
  • 12 Bertina RM, Koeleman BPC, Koster T, Rosendaal FR, Dirven RJ, de Rhonde H, van der Velden PA, Reitsma RH. Mutation in blood coagulation factor V associated with resistance to activated protein C.. Nature 1994; 369: 64-7.
    CrossrefPubMedGoogle Scholar
  • 13 Bertina RM, Reitsma RH, Rosendaal FR, Vandenbroucke JP. Resistance to activated protein C and factor V Leiden as risk factors for venous thrombosis.. Thromb Haemost 1995; 74: 449-553.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 14 Rosendaal FR, Koster T, Vandenbroucke JP, Reitsma PH. High risk of thrombosis in patients homozygous for factor V Leiden (APC resistance).. Blood 1995; 85: 1505-8.
    PubMedGoogle Scholar
  • 15 Kang SS, Wong PWK, Susmano A, Sora J, Norusis M, Ruggie N. Thermolabile methylenetetrahydrofolate reductase: an inherited risk factor for coronary artery disease.. Am J Hum Genet 1991; 48: 536-45.
    PubMedGoogle Scholar
  • 16 Frosst P, Blom HJ, Milos R, Goyette P, Sheppard CA, Matthews RG, Boers GJH, den Heijer M, Kluijtmans LAJ, van den Heuvel LP, Rozen R. A candidate genetic risk factor for vascular disease: a common mutation in methylenetetrahydrofolate reductase.. Nature Genetics 1995; 10: 111-3.
    CrossrefPubMedGoogle Scholar
  • 17 van der Put NM, Sttegers-Theunissen RPM, Frosst P, Trijbels FJM, Eskes TKAB, van den Heuvel LP, Mariman ECM, den Heyer M, Rozen R, Blom HJ. Mutated methyleneterahydrofolate reductase as a risk factor for spina bifada.. Lancet 1995; 346: 1070-1.
    CrossrefPubMedGoogle Scholar
  • 18 Kluijtmans LAJ, van den Heuvel LP, Boers GHJ, Frosst P, Stevens EMB, Denheeijer M, Trijbels FJM, Rozen R, Blom HJ. Molecular genetic analysis in mild hyperhomocysteinemia: a common mutation in the methylene-tetrahydrofolate reductase gene is a genetic risk factor for cardiovascular disease.. Am J Hum Genet 1995; 58: 35-41.
    PubMedGoogle Scholar
  • 19 Wilcken DEL, Wilcken B. The pathogenesis of coronary artery disease: a possible role for methionine metabolism.. J Clin Invest 1976; 57: 1079-82.
    CrossrefPubMedGoogle Scholar
  • 20 Boers GHJ, Smals AGH, Trijbels JMF, Fowler B, Bakkeren JAJM, Schoonderwalt HC, Kleijer WJ, Kloppenborg PWC. Heterozygosity for homocystinuria in premature peripheral and cerebral occlusive arterial disease.. New Engl J Med 1985; 313: 709-15.
    CrossrefPubMedGoogle Scholar
  • 21 Malinow MR. Homocyst(e)ine and arterial occlusive diseases.. J Intern Med 1994; 236: 603-17.
    CrossrefPubMedGoogle Scholar
  • 22 Heijer MD, Blom HJ, Gerrits WBJ, Rosendaal FR, Haak HL, Wijermans PW, Bos GMJ. Is hyperhomocysteinaemia a risk factor for recurrent venous thrombosis?. Lancet 1995; 345: 882-5.
    CrossrefPubMedGoogle Scholar
  • 23 Ocal IT, Sadeghi A, Press RD. Risk of venous thrombosis in carriers of a common mutation in the homocysteine regulatory enzyme methylene-tetrahydrofolate reductase.. Molecular Diagnosis 1997; 2: 61-8.
    CrossrefPubMedGoogle Scholar
  • 24 Kirschbaum NE, Foster PA. The polymerase chain reaction with sequence specific primers for the detection of the factor V mutation associated with activated protein C resistance.. Thromb Haemost 1995; 74: 874-8.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 25 Hezard N, Cornillet-Lefebvre P, Gillot L, Potron G, Nguyen P. Multiplex ASA PCR for a simutaneous determination of factor V Leiden gene, G→A 20210 prothrombin gene, and C→T MTHFR gene mutations.. Thromb Haemost 1998; 79: 1054-5.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 26 Ripoll L, Paulin D, Thomas S, Drouer LO. Multiplex PCR-mediated site directed mutagenesis for one-step determination of factor V Leiden and G20210A transition of the prothrombin gene.. Thromb Haemost 1997; 78: 960-1.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 27 Gomez E, van der Poel SCPAM, Jansen JH, van der Reijden BA, Lowen-berg B. Rapid simutaneous screening of factor V Leiden and G20210A variant by multiplex polymerase chain reaction on whole blood.. Blood 1998; 91: 2208-11.
    PubMedGoogle Scholar
  • 28 Bowen DJ, Bowley S, John M, Collins PW. Factor V Leiden (G1691A), the prothrombin 3"-untranslated region variant (G20210A) and thermolabile methylenetetrahydrofolate reductase (C677T): A single genetic test genotypes at all three loci – Determination of frequencies in the S. Wales population of the UK.. Thromb Haemost 1998; 79: 949-54.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 29 Arruda VR, Annichino-Bizzacchi JM, Goncalves MS, Costa FF. Prevalence of the prothrombin gene variant (nt20210A) in venous thrombosis and arterial disease.. Thromb Haemost 1997; 78: 1430-3.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 30 Rees DC, Cox M, Clegg JB. World distribution of factor V Leiden.. Lancet 1995; 346: 1133-4.
    CrossrefPubMedGoogle Scholar
  • 31 Rees DC. The population genetics of factor V Leiden (Arg506Gln).. Br J Haematol 1996; 95: 579-86.
    CrossrefPubMedGoogle Scholar
  • 32 Ridker PM, Hennekens CH, Lindpainter K, Stampfer MJ, Eisenberg PR, Miletich JP. Mutation in the gene coding for coagulation factor V and the risk of myocardial infarction, stroke, and venous thrombosis in apparently healthy men.. New Engl J Med 1995; 332: 912-7.
    CrossrefPubMedGoogle Scholar
  • 33 Pepe G, Rickards O, Vanegas OC, Brunelli T, Gori AM, Giusti B, Attanasio M, Prisco D, Gensini GF, Abbate R. Prevalence of factor V mutation in non-European populations.. Thromb Haemost 1997; 77: 329-31.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 34 Takamiya O, Ishida F, Kodaira H, Kitano K. APC-resistance and Mnl 1 genotype (Gln 506) of coagulation factor V are rare in Japanese population.. Thromb Haemost 1995; 74: 996
    Article in Thieme ConnectPubMedGoogle Scholar
  • 35 Arruda VR, Zuben PM v, Soares MCP, Menezes R, Annichino-Bizzachi JM, Costa FF. Very low incidence of factor VArg506→Gln in the factor V gene among the Amazonian Indians and the Brazilian black population.. Thromb Haemost 1996; 75: 860-1.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 36 Pottinger P, Sigurdsson F, Berliner N. Detection of factor V Leiden in a nonselected black population.. Blood 1996; 78: 2091.
    PubMedGoogle Scholar
  • 37 Sacchi E, Tagliabue L, Duca F, Mannucci PM, Bianchi A. High frequency of the C677T mutation in the methylenetetrahydrofolate reductase (MTHFR) gene in northern Italy.. Thromb Haemost 1997; 78: 963.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 38 Wilcken DE, Wang XL, Sim AS, McCredie RM. Distribution in healthy and coronary populations of the methylenetetrahydrofolate reductase (MTHFR) C677T mutation.. Arterioscler Thromb Vasc Biol 1996; 16:: 878-82.
    CrossrefPubMedGoogle Scholar
  • 39 Heijer MD, Koster T, Blom HJ, Bos GMJ, Briet E, Reitsma PH, Vandenbrouck JP, Rosendaal FR. Hyperhomocysteinaemia as a risk factor for deep vein thrombosis. New Engl J Med 1996; 334:: 759-62.
    CrossrefPubMedGoogle Scholar