C677T methylenetetrahydrofolate reductase gene polymorphism as a risk factor involved in venous thromboembolism: A population-based case-control study

Yin,Guancheng; Yan,Liqing; Zhang,Zhifeng; Chen,Kebiao; Jin,Xing

doi:10.3892/mmr.2012.1086

C677T methylenetetrahydrofolate reductase gene polymorphism as a risk factor involved in venous thromboembolism: A population-based case-control study

Authors:
- Guancheng Yin
- Liqing Yan
- Zhifeng Zhang
- Kebiao Chen
- Xing Jin
View Affiliations

Affiliations: Department of Vascular Surgery, Shandong Provincial Hospital, Shandong University, Jinan 250012, P.R. China, Department of Cardiovascular Surgery, The Central Hospital of Taian, Taian 271000, P.R. China, Department of Laboratory, The Central Hospital of Taian, Taian 271000, P.R. China
Published online on: September 18, 2012 https://doi.org/10.3892/mmr.2012.1086
Pages: 1271-1275

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

The aim of the current study was to investigate the possible correlation between the C677T methylenetetrahydrofolate reductase (MTHFR) polymorphism and venous thromboembolism (VTE) in a population-based case-control study. Homocysteine (Hcy) was quantified by Abbott IMx immunoassay; screening for C677T MTHFR substitution was performed by polymerase chain reaction (PCR) and restriction analysis. The results from the two groups (440 patients and 440 controls) revealed that the frequency of T alleles and TT carriers was significantly higher in patients compared with that of the healthy controls. The plasma levels of Hcy in the VTE group (13.05±2.37 µmol/l) were significantly higher compared with those in the control group (11.94±2.03 µmol/l, P<0.001). The C677T MTHFR polymorphism is suggested to be associated with the risk for VTE. Plasma levels of Hcy were raised in individuals with the homozygous MTHFR 677TT genotype. In conclusion, the results of the current study suggest that hyperhomocysteinemia and the homozygous 677TT MTHFR genotype are risk factors for VTE.

View Figures

View References

1	Cattaneo M: Hyperhomocysteinemia and venous thromboembolism. Semin Thromb Hemost. 32:716–723. 2006. View Article : Google Scholar : PubMed/NCBI
2	Božič-Mijovski M: Hyperhomocysteinemia and thrombophilia. Clin Chem Lab Med. 48(Suppl 1): S89–S95. 2010.
3	Aguilar B, Rojas JC and Collados MT: Metabolism of homocysteine and its relationship with cardiovascular disease. J Thromb Thrombolysis. 18:75–87. 2004. View Article : Google Scholar : PubMed/NCBI
4	Franchini M, Veneri D, Salvagno GL, Manzato F and Lippi G: Inherited thrombophilia. Crit Rev Clin Lab Sci. 43:249–290. 2006. View Article : Google Scholar
5	Melo SS, Persuhn DC, Meirelles MS, Jordao AA and Vannucchi H: G1793A polymorphisms in the methylenetetrahydrofolate gene: effect of folic acid on homocysteine levels. Mol Nutr Food Res. 50:769–774. 2006. View Article : Google Scholar : PubMed/NCBI
6	Kumar J, Garg G, Kumar A, et al: Single nucleotide polymorphisms in homocysteine metabolism pathway genes: association of CHDH A119C and MTHFR C677T with hyperhomocysteinemia. Circ Cardiovasc Genet. 2:599–606. 2009. View Article : Google Scholar
7	Legnani C, Palareti G, Grauso F, et al: Hyperhomocyst(e)inemia and a common methylenetetrahydrofolate reductase mutation (Ala223Val MTHFR) in patients with inherited thrombophilic coagulation defects. Arterioscler Thromb Vasc Biol. 17:2924–2929. 1997. View Article : Google Scholar
8	D’Angelo A, Mazzola G and Fermo I: Gene-gene and gene-environment interactions in mild hyperhomocysteinemia. Pathophysiol Haemost Thromb. 33:337–341. 2003.PubMed/NCBI
9	Frosst P, Blom HJ, Milos R, et al: A candidate genetic risk factor for vascular disease: a common mutation in methylenetetrahydrofolate reductase. Nat Genet. 10:111–113. 1995. View Article : Google Scholar : PubMed/NCBI
10	Frederiksen J, Juul K, Grande P, Jensen GB, Schroeder TV, Tybjaerg-Hansen A and Nordestgaard BG: Methylenete-trahydrofolate reductase polymorphism (C677T), hyperhomocysteinemia, and risk of ischemic cardiovascular disease and venous thromboembolism: prospective and case-control studies from the Copenhagen City Heart Study. Blood. 104:3046–3051. 2004. View Article : Google Scholar
11	Khare A, Ghosh K, Kulkarni B and Mohanty D: Thrombophilia: hereditary and acquired in cardiovascular disease. Haematologia (Budap). 32:293–311. 2002.PubMed/NCBI
12	Greer IA: Inherited thrombophilia and venous thromboembolism. Best Pract Res Clin Obstet Gynaecol. 17:413–425. 2003. View Article : Google Scholar : PubMed/NCBI
13	Martinelli I: Risk factors in venous thromboembolism. Thromb Haemost. 86:395–403. 2001.PubMed/NCBI
14	Bereczky Z, Kovács KB and Muszbek L: Protein C and protein S deficiencies: similarities and differences between two brothers playing in the same game. Clin Chem Lab Med. 48(Suppl 1): S53–S66. 2010. View Article : Google Scholar : PubMed/NCBI
15	Castoldi E and Rosing J: APC resistance: biological basis and acquired influences. J Thromb Haemost. 8:445–453. 2010. View Article : Google Scholar : PubMed/NCBI
16	Slavik L, Krcova V, Hlusi A, et al: Molecular pathophysiology of thrombotic states and their impact to laboratory diagnostics. Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub. 153:19–25. 2009. View Article : Google Scholar : PubMed/NCBI
17	Simioni P, Scudeller A and Girolami A: Factor V Leiden and thrombophilia. N Engl J Med. 332:13821995.
18	Nguyen A: Prothrombin G20210A polymorphism and thrombophilia. Mayo Clin Proc. 75:595–604. 2000. View Article : Google Scholar : PubMed/NCBI
19	Hoţoleanu C, Porojan-Iuga M, Rusu ML and Andercou A: Hyperhomocysteinemia: clinical and therapeutical involvement in venous thrombosis. Rom J Intern Med. 45:159–164. 2007.PubMed/NCBI
20	Van Oijen MG, Vlemmix F, Laheij RJ, Paloheimo L, Jansen JB and Verheugt FW: Hyperhomocysteinaemia and vitamin B12 deficiency: the long-term effects in cardiovascular disease. Cardiology. 107:57–62. 2007.PubMed/NCBI
21	Aksoy M, Basar Y, Salmayenli N, et al: Hyperhomocysteinemia in patients with arterial occlusive disease. Surg Today. 36:327–331. 2006. View Article : Google Scholar : PubMed/NCBI
22	Ramakrishnan S, Sulochana KN, Lakshmi S, Selvi R and Angayarkanni N: Biochemistry of homocysteine in health and diseases. Indian J Biochem Biophys. 43:275–283. 2006.PubMed/NCBI
23	Cortese C and Motti C: MTHFR gene polymorphism, homocysteine and cardiovascular disease. Public Health Nutr. 4:493–497. 2001. View Article : Google Scholar : PubMed/NCBI
24	Gemmati D, Serino ML, Trivellato C, Fiorini S and Scapoli GL: C677T substitution in the methylenetetrahydrofolate reductase gene as a risk factor for venous thrombosis and arterial disease in selected patients. Haematologica. 84:824–828. 1999.PubMed/NCBI
25	Couturaud F, Oger E, Abalain JH, et al: Methylenetetrahydrofolate reductase C677T genotype and venous thromboembolic disease. Respiration. 67:657–661. 2000. View Article : Google Scholar : PubMed/NCBI
26	Salomon O, Steinberg DM, Zivelin A, et al: Single and combined prothrombotic factors in patients with idiopathic venous thromboembolism: prevalence and risk assessment. Arterioscler Thromb Vasc Biol. 19:511–518. 1999. View Article : Google Scholar : PubMed/NCBI
27	Oger E, Lacut K, Le Gal G, et al; EDITH COLLABORATIVE STUDY GROUP. Hyperhomocysteinemia and low B vitamin levels are independently associated with venous thromboembolism: results from the EDITH study: a hospital-based case-control study. J Thromb Haemost. 4:793–799. 2006. View Article : Google Scholar : PubMed/NCBI
28	Ray JG, Shmorgun D and Chan WS: Common C677T polymorphism of the methylenetetrahydrofolate reductase gene and the risk of venous thromboembolism: meta-analysis of 31 studies. Pathophysiol Haemost Thromb. 32:51–58. 2002. View Article : Google Scholar : PubMed/NCBI