We investigated the prevalence of a genetic variation in the 5,10-methylenetetrahydrofolate reductase (MTHFR) gene (C677T) using polymerase chain reaction techniques in a sample of 500 general Thai population and among 40 unselected Thai patients with an objectively confirmed history of deep vein thrombosis (DVT). The prevalence of the mutated homozygous and heterozygous C677T MTHFR genotype in the group of 500 healthy Thai population was 1.4 and 25.6%, respectively (allele frequency of 14.2%). Of the 40 patients studied, none were homozygotes and 15% were heterozygotes for the C677T MTHFR gene mutation (allele frequency of 7.5%). There was no significant difference in genotype frequency between patients and control groups (p = 0.09). Odds ratios for the probability of the C677T MTHFR gene mutation in the patient versus control group were 0.49 (95% CI 0.21–1.12). These data indicated that the C677T MTHF gene mutation was not associated with DVT in the Thai population. The lower frequency of the C677T MTHFR gene mutation in our Thai population compared with reports from other studies suggests a wide heterogeneity in the 677T MTHFR genotype frequencies of the different ethnic populations even among Asians.

1.
Goldhaber SZ: Epidemiology of pulmonary embolism and deep vein thrombosis; in Tuddenham EGD, Bloom AL, Forbes CD, Thomas DP (eds): Haemostasis and Thrombosis, ed 3. Edinburgh, Churchill Livingstone, 1994, pp 1327–1333.
2.
Anderson FA Jr, Wheeler HB, Goldberg RJ, Hosmer DW, Patwardhan NA, Jovanovic B, Forcier A, Dalen JE: A population-based perspective of the hospital incidence and case-fatality rates of deep vein thrombosis and pulmonary embolism. Arch Intern Med 1991;151:933–938.
3.
Kniffin WD Jr, Baron JA, Barrett J, Birkmeyer JD, Anderson FA Jr: The epidemiology of diagnosed pulmonary embolism and deep venous thrombosis in the elderly. Arch Intern Med 1994;154:861–866.
4.
Rosendaal FR: Risk factors for venous thrombosis. Thromb Haemost 1999;82:610–619.
5.
Seligsohn U, Zivelin A: Thrombophilia as a multigenic disorder. Thromb Haemost 1997;78:297–301.
6.
Atichartakarn V, Pathepchotiwong K, Keorochana S, Eurvilaichit C: Deep vein thrombosis after hip surgery among Thai. Arch Intern Med 1988;148:1349–1353.
7.
Atichartakarn V, Songsiridej N, Jootar S: Incidence and risk factors of deep vein thrombosis among Thai patients: Their implications on patients’ management. J Med Assoc Thai 1988;71:231–237.
8.
Talalak P: Thromboembolism in Thailand: Incidence, coagulogram and its significance in therapeutic implication and prognosis. J Med Assoc Thai 1976;59:6–11.
9.
Chumnijarakit T, Poshyachinda V: Postoperative thrombosis in Thai women. Lancet 1975;1:1357–1358.
10.
Phornphibulaya P, Buranapong P, Ruksawin N, Viranuvatti J: The incidence of postoperative deep vein thrombosis in Thais. J Med Assoc Thai 1984;67:377–381.
11.
Lane DA, Mannucci PM, Bauer KA, Bertina RM, Bochkov NP, Bouyienkov V, Chandy M, Dahlbäck B, Ginter EK, Miletich JP, Rosendaal FR, Seligsohn U: Inherited thrombophilia: Part I. Thromb Haemost 1996;76:651–662.
12.
De Stefano V, Finazzi G, Mannucci PM: Inherited thrombophilia. Pathogenesis, clinical syndromes and management. Blood 1996;154:861–866.
13.
Poort SR, Rosendaal FR, Reitsma PH, Bretina RM: A common genetic variation in the 3′-untranslated region of the prothombin levels and an increase in venous thrombosis. Blood 1996;88:3698–3703.
14.
Angchaisuksiri P, Pingsuthiwong S, Aryuchai K, Busabaratana M, Sura T, Atichartakarn V, Sritara P: Low prevalence of the G1691A mutation in the factor V Gene (factor V Leiden) and the G20210A prothrombin gene mutation in Thai population. Thromb Haemost 1999;Suppl:185–186.
15.
Cattaneo M: Hyperhomocysteinemia, atherosclerosis and thrombosis. Thromb Haemost 1999; 81:165–176.
16.
Hankey G, Ikelboom JW: Homocysteine and vascular disease. Lancet 1999;354:407–413.
17.
Kang SS, Zhou J, Wong PWK, Kowalisyn J, Strokosch G: Intermediate homocysteinemia: A thermolabile variant of methylenetetrahydrofolate reductase. Am J Hum Genet 1988;43:414–421.
18.
Frosst P, Blom HJ, Milos R, Goyette P, Sheppard CA, Matthews RG, Boers GJH, den Heijer M, Kluijtman LAJ, van den Heuvel, Rozen R: A candidate genetic risk factor for vascular disease: A common mutation in methylenetetrahydrofolate reductase. Nat Genet 1995;10:111–113.
19.
Alhenc-Gelas M, Arnaud E, Nicaud V, Aubry ML, Fiessinger JN, Aiach M, Emmerich J: Venous thromboembolic disease and the prothrombin, methylenetetrahydrofolate reductase, and factor V genes. Thromb Haemost 1999;81:506–510.
20.
Kluijtman LAJ, den Heijer M, Reitsma PH, Heil SG, Blom HJ, Rosendaal FR: Thermolabile methylenetetrahydrofolate reductase and factor V Leiden in the risk of deep-vein thrombosis. Thromb Haemost 1998;79:254–258.
21.
Franco RF, Araujo AG, Guerreiro JF, Elion J, Zago MA: Analysis of the 677 CT mutation of the methylenetetrahydrofolate reductase gene in different ethnic groups. Thromb Haemost 1998;79:119–121.
22.
Brown K, Luddington R, Baglin T: Effect of the MTHFR C677T variant on risk of venous thromboembolism: interaction with factor V Leiden and prothrombin (F2 G20210A) mutations. Br J Haematol 1998;103:42–44.
23.
Tosetto A, Missiaglia E, Frezzato M, Rodeghiero F: The VITA project: C677T mutation in the methylene-tetrahydrofolate reductase gene and risk of venous thromboembolism. Br J Haematol 1997;97:804–806.
24.
Hessner MJ, Luhm RA, Pearson SL, Endean DJ, Friedman KD, Montgomery RR: Prevalence of prothrombin G20210A, factor V G1691 (Leiden), and methylenetetrahydrofolate reductase (MTHFR) C677T in seven different populations determined by multiplex allele-specific PCR. Thromb Haemost 1999;81:733–738.
25.
Arruda VR, von Zuben PM, Chiaparini LC, Annichino-Bizzacchi JM, Costa FF: The mutation Ala677 to Val in the methylene tetrahydrofolate reducatase gene: A risk factor for arterial disease and venous thrombosis. Thromb Haemost 1997;77:818–821.
26.
Margaglione M, D’Addedda M, Giuliani N, Cappucci G, Iannaccone L, Vecchione G, Grandone E, Brancaccio V, Di Minno G: The methylenetetrahydrofolate reductase TT677 genotype is associated with venous thrombosis independently of the coexistence of the FV Leiden and the prothrombin A20210 mutation. Thromb Haemost 1998;79:907–911.
27.
Salamon O, Dardik R, Zivelin A, Inbal A, Varon D, Martinowitz U, Mani A, Seligsohn U: Homozygous methylenetetrahydrofolate reductase thermolability (MTHFR-T) is an independent risk factor for idiopathic deep-vein thrombosis (DVT). Thromb Haemost 1997;suppl:568–569.
28.
Cattaneo M, Tsai MY, Bucciarelli P, Taioli E, Zighetti ML, Bignell M, Mannucci PM: A common mutation in the methylenetetrahydrofolate reductase gene (C677T) increases the risk for deep-vein thrombosis in patients with mutant factor V (factor V:Q506). Arterioscler Thromb Vasc Biol 1997;17:1662–1666.
29.
Salden A, Keeney S, Hay CRM, Cumming AM: The C677T MTHFR variant and the risk of venous thrombosis. Br J Haematol 1997;99:464–472.
30.
Sambrook J, Frotsch EF, Maniatis T: In Ford N, Nolan C, Ferguson M, (eds): Molecular Cloning. New York, Cold Spring Harbor Laboratory Press, 1989, pp 9.16–9.19.
31.
Falcon CR, Cattaneo M, Panzeri D, Martinelli I, Mannucci PM: High prevalence of hyperhomocyst(e)inemia in patients with juvenile venous thrombosis. Arterioscler Thromb 1994;14:1080–1083.
32.
den Hejier M, Blom HJ, Gerrits WBJ, Rosendaal FR, Haak HL, Wijermans PW, Bos GMJ: Is hyperhomocysteinaemia a risk factor for recurrent venous thrombosis? Lancet 1995;345:882–885.
33.
Ferom I, Vigano-D’Angelo S, Paroni R, Mazzola G, Calori G, D’Aagelo A: Prevalence of moderate hyperhomocysteinemia in patients with early onset venous and arterial occlusive disease. Ann Intern Med 1995;123:747–753.
34.
Cattaneo M, Martinelli I, Mannucci PM: Hyperhomocysteinemia as a risk factor for deep-vein thrombosis. N Engl J Med 1996;335:974–975.
35.
Brattstrom L, Tengborn L, Lagerstedt C, Israelsson B, Hultberg BL: Plasma homocysteine in venous thrombosis. Haemostasis 1991;21;51–57.
36.
Mudd HS, Skovby F, Levy HL, Pettigrew KD, Wilcken B, Pyeritz RE, Andria G, Boers GHJ, Bromberg IL, Cerone R, Fowler B, Grobe H, Schmidt H, Schweitzer L: The natural history of homocystinuria due to cystathionine β-syntase deficiency. Am J Hum Genet 1985;37:1–31.
37.
Ray JG: Meta-analysis of hyperhomocysteinemia as a risk factor for venous thromboembolic disease. Arch Intern Med 1998;158:2101–2116.
38.
Kluijtmans LAJ, Van den Heuvel LPWJ, Stevens EMB, Frosst P, Van Oost BA, Trijbels JMF, Rozen R, Blom HJ: Molecular genetic analysis in mild hyperhomocysteinemia: A common mutation in the methylenetetrahydrofolate reductase gene is a genetic risk factor for cardiovascular disease. Am J Hum Genet 1996;58:35–41.
39.
Jacques PF, Bostom AG, Williams RR, Ellison RC, Eckfeldt JH, Rosenberg IH, Selhub J, Rozen R: Relation between folate status, a common mutation in methylenetetrahydrofolate reductase, and plasma homocysteine concentrations. Circulation 1996;93:7–9.
40.
Van der Put NMJ, Van Den Heuvel LPWJ, Steegers-Theunissen RPM, Trijbels JMF, Eskes TKAB, Mariman ECM, Den Heijer M, Blom HJ: Decreased methylenetetrahydrofolate reductase activity due to the 677C → T mutation in families with spina bifida offspring. J Mol Med 1996;74:691–694.
41.
den Heijer M, Blom HJ, Gerrits WBJ, Rosendaal FR, Haak HL, Wijermans PW, Bos GMJ: Hyperhomocysteinemia as a risk factor for deep-vein thrombosis. N Engl J Med 1996;334:759–762.
42.
Van der Put NMJ, Steegers-Theunissen RPM, Frosst P, Trijbels JMF, Eskes TKAB, Van den Heuvel LPWJ, Mariman ECM, Den Heijer M, Rozen R, Blom HJ: Mutated methylenetetrahydrofolate reductase as a risk factor for spina bifida. Lancet 1995;346:1070–1071.
43.
Fryer RH, Wilson BD, Gubler DB, Fitzgerald LA, Rodgers GM: Homocysteine, a risk factor for premature vascular disease and thrombosis, induces tissue factor activity in endothelial cells. Arterioscler Thromb 1993;13:1327–1333.
44.
Rodgers GM, Conn MT: Homocysteine, an atherogenic stimulus, reduces protein C activation by arterial and venous endothelial cells. Blood 1990;75:895–901.
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.