Skip to main content

Advertisement

Log in

Quantitative Assessment of Association Between rs1801133 Polymorphism and Susceptibility to Stroke

  • Original Paper
  • Published:
Cell Biochemistry and Biophysics Aims and scope Submit manuscript

Abstract

Methylenetetrahydrofolate reductase (MTHFR) is an important enzyme involved in folate metabolism, which is essential for DNA synthesis and methylation. Genetic variations in the MTHFR gene seem to contribute to a decreased activity of MTHFR, ultimately confer increased susceptibility to stroke. To assess the association between this polymorphism and stroke risk, we conducted a comprehensive meta-analysis based on 73 eligible studies. A total of 73 studies, including 10,225 cases and 13,800 controls identified between 1999 and 2012, were selected through researching the PubMed, MEDLINE, EMBASE, Cochrane Library, Web of Science, and Chinese Biomedical Chinese National Knowledge Infrastructure and Literature database databases. Odds ratios (ORs) with corresponding 95 % confidence intervals (CIs) were used to assess the association. Overall, a significant elevated risk of stroke risk was associated with the rs1801133 polymorphism in all genetic models (homozygote model: OR 1.296, 95 % CI 1.109–1.514; dominant model: OR 1.179, 95 % CI 1.058–1.315; recessive model: OR 1.209, 95 % CI 1.063–1.375; allele comparison model: OR 1.154, 95 % CI 1.061–1.256). In the stratified analyses, significantly increased stroke risks were indicated among Asians in all genetic models (homozygote model: OR 1.726, 95 % CI 1.314–2.267; dominant model: OR 1.535, 95 % CI 1.282–1.838; recessive model: OR 1.452, 95 % CI 1.160–1.818; allele comparison model: OR 1.403, 95 % CI 1.211–1.626).The present meta-analysis suggests that rs1801133 polymorphism contributes to the risk of stroke, of note, in Asian populations.

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.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7

Similar content being viewed by others

References

  1. World Health Organization (WHO). (2004). The atlas of heart disease and stroke. In J. Mackay & G. Mensah (Eds.), Geneva: WHO.

  2. Hassan, A., & Markus, H. S. (2000). Genetics and ischemic stroke. Brain, 123, 1784–1812.

    Article  PubMed  Google Scholar 

  3. Casas, J. P., Hingorani, A. D., Bautista, L. E., & Sharma, P. (2004). Metaanalysis of genetics studies in ischemic stroke. Thirty-two genes involving approximately 18,000 cases and 58,000 controls. Archives of Neurology, 61, 1652–1662.

    Article  PubMed  Google Scholar 

  4. Matthews, R. G., Sheppard, C., & Goulding, C. (1998). Methylenetetrahydrofolate reductase and methionine synthase: Biochemistry and molecular biology. European Journal of Pediatrics, 157, S54–S59.

    Article  CAS  PubMed  Google Scholar 

  5. Engbersen, A. M., Franken, D. G., Boers, G. H., Stevens, E. M., Trijbels, F. J., et al. (1995). Thermolabile 5,10-methylenetetrahydrofolate reductase as a cause of mild hyperhomocysteinemia. American Journal of Human Genetics, 56, 142–150.

    CAS  PubMed Central  PubMed  Google Scholar 

  6. Botto, L. D., & Yang, Q. (2000). 5,10-Methylenetetrahydrofolate reductase gene variants and congenital anomalies: A huge review. American Journal of Epidemiology, 151, 862–877.

    Article  CAS  PubMed  Google Scholar 

  7. Higgins, J., & Thompson, S. G. (2002). Quantifying heterogeneity in a meta-analysis. Statistics in Medicine, 21, 1539–1558.

    Article  PubMed  Google Scholar 

  8. DerSimonian, R., & Laird, N. (1986). Meta-analysis in clinical trials. Control Clinical Trials, 7, 177–188.

    Article  CAS  Google Scholar 

  9. Begg, C. B., & Mazumdar, M. (1994). Operating characteristics of a rank correlation test for publication bias. Biometrics, 50, 1088–1101.

    Article  CAS  PubMed  Google Scholar 

  10. Egger, M., Smith, G. D., Schneider, M., & Minder, C. (1997). Bias in meta-analysis detected by a simple, graphical test. BMJ, 315, 629–634.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  11. Duca, F., Sacchi, E., Taglibue, L., & Tajoli, E. (1997). C677T methylenetetrahydrofolate reductase (MTHFR) mutation in stroke [abstract]. Thrombosis and Haemostasis, 78, 102.

    Google Scholar 

  12. Markus, H. S., Ali, N., Swaminathan, R., Sankaralingam, A., Molloy, J., et al. (1997). A common polymorphism in the methylenetetrahydrofolate reductase gene, homocysteine, and ischemic cerebrovascular disease. Stroke, 28(9), 1739–1743.

    Article  CAS  PubMed  Google Scholar 

  13. Kostulas, K., Crisby, M., Huang, W. X., Lannfelt, L., Hagenfeldt, L., et al. (1998). A methylenetetrahydrofolate reductase gene polymorphism in ischaemic stroke and in carotid artery stenosis. European Journal of Clinical Investigation, 28(4), 285–289.

    Article  CAS  PubMed  Google Scholar 

  14. Salooja, N., Catto, A., Carter, A., Tudenham, E. G., & Grant, P. J. (1998). Methylene tetrahydrofolate reductase C677T genotype and stroke. Clinical and Laboratory Haematology, 20(6), 357–361.

    Article  CAS  PubMed  Google Scholar 

  15. Nakata, Y., Katsuya, T., Takami, S., Sato, N., Fu, Y., et al. (1998). Methylenetetrahydrofolate reductase gene polymorphism: Relation to blood pressure and cerebrovascular disease. American Journal of Hypertension, 11(8Pt 1), 1019–1023.

  16. Morita, H., Kurihara, H., Tsubaki, S., Sugiyama, T., Hamada, C., et al. (1998). Methylenetetrahydrofolate reductase gene polymorphism and ischemic stroke in Japanese. Arteriosclerosis, Thrombosis, and Vascular Biology, 18(9), 1465–1469.

    Article  CAS  PubMed  Google Scholar 

  17. Reuner, K. H., Ruf, A., Kaps, M., Druschky, K. F., & Patscheke, H. (1998). The mutation C677T in the methylene tetrahydrofolate reductase gene and stroke. Thrombosis and Haemostasis, 79(2), 450–451.

    CAS  PubMed  Google Scholar 

  18. Margaglione, M., D’Andrea, G., Giuliani, N., Brancaccio, V., De Lucia, D., et al. (1997). Inherited prothrombotic conditions and premature ischemic stroke: Sex difference in the association with factor V Leiden. Arteriosclerosis, Thrombosis, and Vascular Biology, 19(7), 1751–1756.

    Article  Google Scholar 

  19. Harmon, D. L., Doyle, R. M., Meleady, R., Doyle, M., Shields, D. C., et al. (1999). Genetic analysis of the thermolabile variant of 5, 10-methylenetetrahydrofolate reductase as a risk factor for ischemic stroke. Arteriosclerosis, Thrombosis, and Vascular Biology, 19(2), 208–211.

    Article  CAS  PubMed  Google Scholar 

  20. Gaustadnes, M., Rüdiger, N., Møller, J., Rasmussen, K., Bjerregaard Larsen, T., & Ingerslev, J. (1999). Thrombophilic predisposition in stroke and venous thromboembolism in Danish patients. Blood Coagulation & Fibrinolysis, 10(5), 251–259.

    Article  CAS  Google Scholar 

  21. Lalouschek, W., Aull, S., Serles, W., Schnider, P., Mannhalter, C., et al. (1999). C677T MTHFR mutation and factor V Leiden mutation in patients with TIA/minor stroke: A case-control study. Thrombosis Research, 93(2), 61–69.

    Article  CAS  PubMed  Google Scholar 

  22. Notsu, Y., Nabika, T., Park, H. Y., Masuda, J., & Kobayashi, S. (1999). Evaluation of genetic risk factors for silent brain infarction. Stroke, 30(9), 1881–1886.

    Article  CAS  PubMed  Google Scholar 

  23. Press, R. D., Beamer, N., Evans, A., DeLoughery, T. G., & Coull, B. M. (1999). Role of a common mutation in the homocysteine regulatory enzyme methylenetetrahydrofolate reductase in ischemic stroke. Diagnostic Molecular Pathology, 8(1), 54–58.

    Article  CAS  PubMed  Google Scholar 

  24. Akar, N., Akar, E., Deda, G., Sipahi, T., & Orsal, A. (1999). Factor V1691G-A, prothrombin 20210 G-A, and methylenetetrahydrofolate reductase 677 C-T variants in Turkish children with cerebral infarct. Journal of Child Neurology, 14, 749–751.

    Article  CAS  PubMed  Google Scholar 

  25. Nowak-Göttl, U., Sträter, R., Heinecke, A., Junker, R., Koch, H. G., et al. (1999). Lipoprotein (a) and genetic polymorphisms of clotting factor V, prothrombin, and methylenetetrahydrofolate reductase are risk factors of spontaneous ischemic stroke in childhood. Blood, 94, 3678–3682.

    PubMed  Google Scholar 

  26. McColl, C., Rafferty, I., McWilliam, R., & Eunson, P. (1999). Factor V Leiden, prothrombin 20210G > A and the MTHFR C677T mutations in childhood stroke. Thrombosis and Haemostasis, 81, 690–694.

    CAS  PubMed  Google Scholar 

  27. Cardo, E., Monros, E., Colome, C., Artuch, R., Campistol, J., et al. (2000). Children with stroke: Polymorphism of the MTHFR gene, mild hyperhomocysteinemia, and vitamin status. Journal of Child Neurology, 15, 295–298.

    Article  CAS  PubMed  Google Scholar 

  28. Kenet, G., Sadetzki, S., Murad, H., Martinowitz, U., Rosenberg, N., et al. (2000). Factor V Leiden and antiphospholipid antibodies are significant risk factors for ischemic stroke in children. Stroke, 31, 1283–1288.

    Article  CAS  PubMed  Google Scholar 

  29. Yoo, J. H., & Park, S. C. (2000). Low plasma folate in combination with the 677 C → T methylenetetrahydrofolate reductase polymorphism is associated with increased risk of coronary artery disease in Koreans. Thrombosis Research, 97(2), 77–84.

    Article  CAS  PubMed  Google Scholar 

  30. Eikelboom, J. W., Hankey, G. J., Anand, S. S., Lofthouse, E., Staples, N., & Baker, R. I. (2000). Association between high homocyst(e)ine and ischemic stroke due to large- and small-artery disease but not other etiologic subtypes of ischemic stroke. Stroke, 31(5), 1069–1075.

    Article  CAS  PubMed  Google Scholar 

  31. Voetsch, B., Damasceno, B. P., Camargo, E. C., Massaro, A., Bacheschi, L. A., et al. (2000). Inherited thrombophilia as a risk factor for the development of ischemic stroke in young adults. Thrombosis and Haemostasis, 83(2), 229–233.

    CAS  PubMed  Google Scholar 

  32. Zheng, Y. Z., Tong, J., Do, X. P., Pu, X. Q., & Zhou, B. T. (2000). Prevalence of methylenetetrahydrofolate reductase C677T and its association with arterial and venous thrombosis in the Chinese population. British Journal of Haematology, 109(4), 870–874.

    Article  CAS  PubMed  Google Scholar 

  33. Prengler, M., Sturt, N., Krywawych, S., Surtees, R., Liesner, R., & Kirkham, F. (2001). Homozygous thermolabile variant of the methylenetetrahydrofolate reductase gene: A potential risk factor for hyperhomocysteinaemia, CVD, and stroke in childhood. Developmental Medicine and Child Neurology, 43(4), 220–225.

    Article  CAS  PubMed  Google Scholar 

  34. Wu, Y., Tomon, M., & Sumino, K. (2001). Methylenetetrahydrofolate reductase gene polymorphism and ischemic stroke: Sex difference in Japanese. Kobe Journal of Medical Sciences, 47(6), 255–262.

    CAS  PubMed  Google Scholar 

  35. Zhang, G., & Dai, C. (2001). Gene polymorphisms of homocysteine metabolism-related enzymes in Chinese patients with occlusive coronary artery or cerebral vascular diseases. Thrombosis Research, 104, 187–195.

    Article  CAS  PubMed  Google Scholar 

  36. Topic, E., Timundic, A. M., Ttefanovic, M., Demarin, V., Vukovic, V., et al. (2001). Polymorphism of apoprotein E (APOE), methylenetetrahydrofolate reductase (MTHFR) and paraoxonase (PON1) genes in patients with cerebrovascular disease. Clinical Chemistry and Laboratory Medicine, 39, 346–350.

    Article  CAS  PubMed  Google Scholar 

  37. Gallai, V., Caso, V., Paciaroni, M., Cardaioli, G., Arning, E., et al. (2001). Mild hyperhomocyst(e)inemia: A possible risk factor for cervical artery dissection. Stroke, 32, 714–718.

    Article  CAS  PubMed  Google Scholar 

  38. Lopaciuk, S., Bykowska, K., Kwiecinski, H., Mickielewicz, A., Czlonkowska, A., et al. (2001). Factor V Leiden, prothrombin gene G20210A variant, and methylenetetrahydrofolate reductase C677T genotype in young adults with ischemic stroke. Clinical and Applied Thrombosis/Hemostasis, 7, 346–350.

    Article  CAS  PubMed  Google Scholar 

  39. McIlroy, S. P., Dynan, K. B., Lawson, J. T., Patterson, C. C., & Passmore, A. P. (2002). Moderately elevated plasma homocysteine, methylenetetrahydrofolate-reductase genotype, and risk for stroke, vascular dementia, and Alzheimer disease in Northern Ireland. Stroke, 33, 2351–2356.

    Article  CAS  PubMed  Google Scholar 

  40. Li, C., Zhang, C., Qiu, S., Lu, X., Zeng, Y., et al. (2002). Polymorphisms of ACE-1 and MTHFR genes and genetic susceptibility of ischemic stroke. Zhonghua Yi Xue Za Zhi, 82, 1046–1049.

    CAS  PubMed  Google Scholar 

  41. Yingdong, Z., Zhigang, Z., & Yang, L. (2002). Association of plasma homocysteine level and N5, N10-methylenetetrahydrofolate reductase gene polymorphism with cerebral infarction. Chinese Medical Sciences Journal, 17, 231–235.

    PubMed  Google Scholar 

  42. Huang, Y., Zhao, Y. Y., & Li, S. (2002). Hyperhomocysteine, methylenetetrahy-drofolate reductase gene, and other risk factors in ischemic stroke. Zhonghua Yi Xue Za Zhi., 82, 119–122.

    CAS  PubMed  Google Scholar 

  43. Szolnoki, Z., Somogyvari, F., Kondacs, A., Szabo, M., & Fodor, L. (2002). Evaluation of the interactions of common genetic mutations in stroke subtypes. Journal of Neurology, 249, 1391–1397.

    Article  CAS  PubMed  Google Scholar 

  44. Barreirinho, S., Ferro, A., Santos, M., Costa, E. L., Pinto-Basto, J., et al. (2003). Inherited and acquired risk factors and their combined effects in pediatric stroke. Pediatric Neurology, 28(2), 134–138.

    Article  PubMed  Google Scholar 

  45. Pezzini, A., Del Zotto, E., Magoni, M., Costa, A., Archetti, S., et al. (2003). Inherited thrombophilic disorders in young adults with ischemic stroke and patent foramen ovale. Stroke, 34(28–33), 48.

    Google Scholar 

  46. Szolnoki, Z., Somogyvari, F., Kondacs, A., Szabo, M., Fodor, L., Bene, J., et al. (2003). Evaluation of the modifying effects of unfavourable genotypes on classical clinical risk factors for ischaemic stroke. Journal of Neurology, Neurosurgery, and Psychiatry, 74, 1615–1620.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  47. Li, Z. H., Sun, L., Zhang, H. Y., Liao, Y. H., Wang, D. W., et al. (2003). Elevated plasmahomocysteine was associated with hemorrhagic and ischemic stroke, butmethylenetetrahydrofolate reductase gene C677T polymorphism was a risk factor for thrombotic stroke—A multicenter case-control study in China. Stroke, 34, 2085–2090.

    Article  CAS  PubMed  Google Scholar 

  48. Choi, B. O., Kim, N. K., Kim, S. H., Kang, M. S., Lee, S., et al. (2003). Homozygous C677T mutation in the MTHFR gene as an independent risk factor for multiple small-artery occlusions. Thrombosis Research, 111, 39–44.

    Article  CAS  PubMed  Google Scholar 

  49. Kelly, P. J., Shih, V. E., Kistler, J. P., Barron, M., Lee, H., et al. (2003). Low vitamin B6, but not homocyst(e)ine, is associated with increased risk of stroke/TIA in the era of folic acid grain fortification. Stroke, 34, e51–e54.

    Article  CAS  PubMed  Google Scholar 

  50. Baum, L., Wong, K. S., Ng, H. K., Tomlinson, B., Rainer, T. H., et al. (2003). Methylenetetrahydrofolate reductase gene A222V polymorphism and risk of ischemic stroke. Clinical Chemistry and Laboratory Medicine, 42(12), 1370–1376.

    Google Scholar 

  51. Uçar, F., Sönmez, M., Ovali, E., Ozmenoglu, M., Karti, S. S., et al. (2004). MTHFR C677T polymorphism and its relation to ischemic stroke in the Black Sea Turkish population. American Journal of Hematology, 76(1), 40–43.

    Article  PubMed  Google Scholar 

  52. Alluri, R. V., Mohan, V., Komandur, S., Chawda, K., Chaudhuri, J. R., & Hasan, Q. (2005). MTHFR C677T gene mutation as a risk factor for arterial stroke: A hospital based study. European Journal of Neurology, 12(1), 40–44.

    Article  CAS  PubMed  Google Scholar 

  53. Linnebank, M., Montenarh, M., Kölsch, H., Linnebank, A., Schnez, K., et al. (2005). Common genetic variants of homocysteine metabolism in ischemic stroke: A case-control study. European Journal of Neurology, 12(8), 614–618.

    Article  CAS  PubMed  Google Scholar 

  54. Fang, X., Namba, H., Akamine, S., & Sugiyama, K. (2005). Methylenetetrahydrofolate reductase gene polymorphisms in patients with cerebral hemorrhage. Neurological Research, 27(1), 73–76.

    Article  CAS  PubMed  Google Scholar 

  55. Kawamoto, R., Kohara, K., Oka, Y., Tomita, H., Tabara, Y., & Miki, T. (2005). An association of 5,10-methylenetetrahydrofolate reductase (MTHFR) gene polymorphism and ischemic stroke. Journal of Stroke and Cerebrovascular Diseases, 14(2), 67–74.

    Article  PubMed  Google Scholar 

  56. Rook, J. L., Nugent, D. J., & Young, G. (2005). Pediatric stroke and methylenetetrahydrofolate reductase polymorphisms: An examination of C677T and A1298C mutations. Journal of Pediatric Hematology/Oncology, 27(11), 590–593.

    Article  PubMed  Google Scholar 

  57. Gao, X., Yang, H., & ZhiPing, T. (2006). Association studies of genetic polymorphism, environmental factors and their interaction in ischemic stroke. Neuroscience Letters, 398(3), 172–177.

    Article  CAS  PubMed  Google Scholar 

  58. Pezzini, A., Grassi, M., Del Zotto, E., Assanelli, D., Archetti, S., et al. (2006). Interaction of homocysteine and conventional predisposing factors on risk of ischaemic stroke in young people: Consistency in phenotype-disease analysis and genotype-disease analysis. Journal of Neurology, Neurosurgery and Psychiatry, 77(10), 1150–1156.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  59. Sazci, A., Ergul, E., Tuncer, N., Akpinar, G., & Kara, I. (2006). Methylenetetrahydrofolate reductase gene polymorphisms are associated with ischemic and hemorrhagic stroke: Dual effect of MTHFR polymorphisms C677T and A1298C. Brain Research Bulletin, 71(1–3), 45–50.

    Article  CAS  PubMed  Google Scholar 

  60. Dikmen, M., Ozbabalik, D., Gunes, H. V., Degirmenci, I., Bal, C., et al. (2006). Acute stroke in relation to homocysteine and methylenetetrahydrofolate reductase gene polymorphisms. Acta Neurologica Scandinavica, 113(5), 307–314.

    Article  CAS  PubMed  Google Scholar 

  61. Komitopoulou, A., Platokouki, H., Kapsimali, Z., Pergantou, H., Adamtziki, E., & Aronis, S. (2006). Mutations and polymorphisms in genes affecting hemostasis proteins and homocysteine metabolism in children with arterial ischemic stroke. Cerebrovascular Diseases, 22(1), 13–20.

    Article  CAS  PubMed  Google Scholar 

  62. Panigrahi, I., Chatterjee, T., Biswas, A., Behari, M., Choudhry, P. V., & Saxena, R. (2006). Role of MTHFR C677T polymorphism in ischemic stroke. Neurology India, 54(1), 48–50.

    Article  PubMed  Google Scholar 

  63. Marie, S. K., Shinjo, S. K., Oba-Shinjo, S. M., da Silva, R., Barbosa, K. C., et al. (2007). Methylenetetrahydrofolate reductase gene polymorphism is not related to the risk of ischemic cerebrovascular disease in a Brazilian population. Clinics (Sao Paulo), 62(3), 295–300.

    Google Scholar 

  64. Sabino, A., Fernandes, A. P., Lima, L. M., Ribeiro, D. D., Sousa, M. O., et al. (2009). Polymorphism in the methylenetetrahydrofolate reductase (C677T) gene and homocysteine levels: A comparison in Brazilian patients with coronary arterial disease, ischemic stroke and peripheral arterial obstructive disease. Journal of Thrombosis and Thrombolysis, 27(1), 82–87.

    Article  CAS  PubMed  Google Scholar 

  65. Kim, O. J., Hong, S. P., Ahn, J. Y., Hong, S. H., Hwang, T. S., et al. (2007). Influence of combined methionine synthase (MTR 2756A > G) and methylenetetrahydrofolate reductase (MTHFR 677C > T) polymorphisms to plasma homocysteine levels in Korean patients with ischemic stroke. Yonsei Medical Journal, 48(2), 201–209.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  66. Berge, E., Haug, K. B., Sandset, E. C., Haugbro, K. K., Turkovic, M., & Sandset, P. M. (2007). The factor V Leiden, prothrombin gene 20210GA, methylenetetrahydrofolate reductase 677CT and platelet glycoprotein IIIa 1565TC mutations in patients with acute ischemic stroke and atrial fibrillation. Stroke, 38(3), 1069–1071.

    Article  CAS  PubMed  Google Scholar 

  67. Shi, C., Kang, X., Wang, Y., & Zhou, Y. (2008). The coagulation factor V Leiden, MTHFRC677T variant and eNOS 4ab polymorphism in young Chinese population with ischemic stroke. Clinica Chimica Acta, 396(1–2), 7–9.

    Article  CAS  Google Scholar 

  68. Sirachainan, N., Sasanakul, W., Visudtibhan, A., Tapanapruksakul, P., Charoenkwan, P., et al. (2008). The effect of polymorphisms of MTHFR C677T, A1298C, MS A2756G and CBS 844ins68 bp on plasma total homocysteine level and the risk of ischemic stroke in Thai children. Thrombosis Research, 122(1), 33–37.

    Article  CAS  PubMed  Google Scholar 

  69. Moe, K. T., Woon, F. P., De Silva, D. A., Wong, P., Koh, T. H., et al. (2008). Association of acute ischemic stroke with the MTHFR C677T polymorphism but not with NOS3 gene polymorphisms in a Singapore population. European Journal of Neurology, 15(12), 1309–1314.

    Article  CAS  PubMed  Google Scholar 

  70. Goracy, I., Cyryłowski, L., Kaczmarczyk, M., Fabian, A., Koziarska, D., et al. (2009). C677T polymorphism of the methylenetetrahydrofolate reductase gene and the risk of ischemic stroke in Polish subjects. Journal of Applied Genetics, 50(1), 63–67.

    Article  CAS  PubMed  Google Scholar 

  71. Herak, D. C., Antolic, M. R., Krleza, J. L., Pavic, M., Dodig, S., et al. (2009). Inherited prothrombotic risk factors in children with stroke, transient ischemic attack, or migraine. Pediatrics, 123(4), e653–e660.

    Article  PubMed  Google Scholar 

  72. Djordjevic, V., Stankovic, M., Brankovic-Sreckovic, V., Rakicevic, L., & Radojkovic, D. (2009). Genetic risk factors for arterial ischemic stroke in children: A possible MTHFR and eNOS gene–gene interplay? Journal of Child Neurology, 24(7), 823–827.

    Article  PubMed  Google Scholar 

  73. Biswas, A., Tiwari, A. K., Ranjan, R., Meena, A., Akhter, M. S., et al. (2009). Prothrombotic polymorphisms, mutations, and their association with pediatric non-cardioembolic stroke in Asian-Indian patients. Annals of Hematology, 88(5), 473–478.

    Article  PubMed  Google Scholar 

  74. Zak, I., Sarecka-Hujar, B., Kopyta, I., Emich-Widera, E., Marszal, E., et al. (2009). The T allele of the 677C > T polymorphism of methylenetetrahydrofolate reductase gene is associated with an increased risk of ischemic stroke in Polish children. Journal of Child Neurology, 24(10), 1262–1267.

    Article  PubMed  Google Scholar 

  75. Morita, D. C., Donaldson, A., Butterfield, R. J., Benedict, S. L., & Bale, J. F., Jr. (2009). Methylenetetrahydrofolate reductase gene polymorphism and childhood stroke. Pediatric Neurology, 41(4), 247–249.

    Article  PubMed  Google Scholar 

  76. Isordia-Salas, I., Barinagarrementería-Aldatz, F., Leaños-Miranda, A., Borrayo-Sánchez, G., Vela-Ojeda, J., et al. (2010). The C677T polymorphism of the methylenetetrahydrofolate reductase gene is associated with idiopathic ischemic stroke in the young Mexican-Mestizo population. Cerebrovascular Diseases, 29(5), 454–459.

    Article  CAS  PubMed  Google Scholar 

  77. Giusti, B., Saracini, C., Bolli, P., Magi, A., Martinelli, I., et al. (2010). Early-onset ischaemic stroke: Analysis of 58 polymorphisms in 17 genes involved in methionine metabolism. Thrombosis and Haemostasis, 104(2), 231–242.

    Article  PubMed  Google Scholar 

  78. Salem-Berrabah, O. B., Mrissa, R., Machghoul, S., Hamida, A. B., N’siri, B., et al. (2010). Hyperhomocysteinemia, C677T MTHFR polymorphism and ischemic stroke in Tunisian patients. La Tunisie Medicale, 88(9), 655–659.

    PubMed  Google Scholar 

  79. They-They, T. P., Nadifi, S., Rafai, M. A., Battas, O., & Slassi, I. (2011). Methylenehydrofolate reductase (C677T) polymorphism and large artery ischemic stroke subtypes. Acta Neurologica Scandinavica, 123(2), 105–110.

    Article  CAS  PubMed  Google Scholar 

  80. Arsene, D., Găină, G., Bălescu, C., & Ardeleanu, C. (2011). C677T and A1298C methylenetetrahydropholate reductase (MTHFR) polymorphisms as factors involved in ischemic stroke. Romanian Journal of Morphology and Embryology, 52(4), 1203–1207.

    CAS  PubMed  Google Scholar 

  81. Somarajan, B. I., Kalita, J., Mittal, B., & Misra, U. K. (2011). Evaluation of MTHFR C677T polymorphism in ischemic and hemorrhagic stroke patients. A case-control study in a Northern Indian population. Journal of the Neurological Sciences, 304(1–2), 67–70.

    Article  CAS  PubMed  Google Scholar 

  82. Mejia Mohamed, E. H., Tan, K. S., Ali, J. M., & Mohamed, Z. (2011). TT genotype of the methylenetetrahydrofolate reductase C677T polymorphism is an important determinant for homocysteine levels in multi-ethnic Malaysian ischaemic stroke patients. Annals of the Academy of Medicine, Singapore, 40(4), 186–191.

    PubMed  Google Scholar 

  83. Sarecka-Hujar, B., Kopyta, I., Pienczk-Reclawowicz, K., Reclawowicz, D., Emich-Widera, E., & Pilarska, E. (2012). The TT genotype of methylenetetrahydrofolate reductase 677C > T polymorphism increases the susceptibility to pediatric ischemic stroke: Meta-analysis of the 822 cases and 1,552 controls. Molecular Biology Reports, 39(8), 7957–7963.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  84. Li, P., & Qin, C. (2014). Methylenetetrahydrofolate reductase (MTHFR) gene polymorphisms and susceptibility to ischemic stroke: A meta-analysis. Gene, 535(2), 359–364.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Guorong Bi.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Zhang, W., Wang, Y. & Bi, G. Quantitative Assessment of Association Between rs1801133 Polymorphism and Susceptibility to Stroke. Cell Biochem Biophys 71, 85–98 (2015). https://doi.org/10.1007/s12013-014-0166-3

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12013-014-0166-3

Keywords

Navigation