Abstract
Hyperhomocysteinemia is reported to be an independent risk factor for the development of ischemic stroke. Several studies on genetic variants of methylenetetrahydrofolate reductase (MTHFR, which plays a crucial role in regulation of plasma homocysteine concentration) reported an association between C677T gene polymorphism and stroke in some Asian populations. No study but one detected this association in Caucasians. The purpose of the present case-control study was to find a relationship betweenMTHFR genotypes and stroke in a Polish population.MTHFR genotypes were determined by PCR in 152 patients with ischemic stroke from northwestern Poland and in 135 consecutive newborns from the same population. The TT genotype and the T allele were significantly more frequent in patients than in the control group (11.8% vs. 4.4%, and 34.5% vs. 21.5%,P < 0.01). When males and females were analyzed separately, the differences were statistically significant in both genders. It is concluded that presence of the T allele is a risk factor for ischemic stroke in Polish subjects.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Adams HP Jr, Bendixen BH, Kappelle LJ, Biller J, Love BB, Gordon DL, et al. 1993. Classification of subtype of acute ischemic stroke: definitions for use in a multicenterclinical trial: TOAST: Trialof Org 10172 in Acute Stroke Treatment. Stroke 24: 35–41.
Alluri RV, Mohan V, Komandur S, Chawda K, Chaudhuri JR, Hasan Q, 2005. MTHFR C677T gene mutation as a risk factor for arterial stroke: a hospital based study. Eur J Neurol 12: 40–44.
Boushey C, Beresford S, Omenn G, Motulsky A, 1995. A quantitative assessment of plasma homocysteine as a risk factor for vascular disease: probable benefits of increasing folic acid intakes. JAMA 274: 1049–1057.
Brattstrom L, Wilcken DE, Ohrvik J, Brudin L, 1998. Common methy lenetetrahydrofolate reductase gene mutation leads to hyperhomocysteinemia but not to vascular disease: theresultof ameta-analysis. Circulation 98: 2520–2526.
Casas JP, Hingorani AD, Bautista LE, Sharma P, 2004. Meta-analysis of genetic studies in ischemic stroke. Thirty-two genes involving approximately 18000 cases and 58000 controls. Arch Neurol 61: 1652–1661.
Dikmen M, Ozbabalik D, Gunes HV, Degirmenci I, Bal C, Ozdemir G, et al. 2006. Acute stroke in relation to homocysteine and methylenetetrahydrofolate reductase gene polymorphisms. Acta Neurol Scand 113: 307–314.
Eikelboom JW, Hankey GJ, Anand SS, Lofthouse E, Staples N, Baker RI, 2000. Association between high homocysteine and ischemic stroke due to large- and small-artery disease but not other etiologic subtypes of ischemic stroke. Stroke 31: 1069–1071.
Freiberger T, Vyskocilova M, Kolarova L, Kuklinek P, Krystufkova O, Lahodna M, et al. 2002. Exon 1 polymorphism of the B2BKR gene does not influence the clinical status of patients with hereditary angioedema. Hum Immunol 63: 492–494.
Frosst P, Blom HJ, Milos R, Goyette P, Sheppard CA, Mathews RG, et al. 1995. A candidate genetic risk factor for vascular disease: a common mutation in methylenetetrahydrofolate reductase. Nat Genet 10: 111–113.
Kalita J, Srivastava R, Bansal V, Agarwal S, Misra UK, 2006. Methylenetetrahydrofolate reductase gene polymorphism in Indian stroke patients. Neurol India 54: 260–263.
Kohara K, Fujisawa M, Ando F, Tabara Y, Niino N, Miki T, et al. 2003. MTHFR gene polymorphism as a risk factor for silent brain infarcts and white matter lesions in the Japanese general population. The NILS-LSA Study. Stroke 34: 1130–1135.
Kostulas K, Crisby M, Huang WX, Lannfelt L, Hagenfeldt L, Eggertsen G, et al. 1998. A methylenetetrahydrofolate reductase gene polymorphism in ischemic stroke and in carotid artery stenosis. Eur J Clin Invest 28: 285–289.
Kristensen B, Malm J, Nilsson N, Hultdin J, Carlberg B, Dahlen G, et al. 1999. Hyper-homocysteinemia and hypofibrinolysis in young adults with ischemic stroke. Stroke 30: 974–980.
Lahiri DK, Bye S, Nurnberger Jr. JI, Hodes ME, Crisp M, 1992. A non-organic and non-enzymatic extraction method gives higher yields of genomic DNA from whole-blood samples than do nine other methods tested. J Biochem Bioph Meth 25: 193–205.
Li Z, Sun L, Zhang H, Liao Y, Wang D, Zhao B, et al. 2003. Elevated plasma homocysteine was associated with hemorrhagic and ischemic stroke, but methylenetetrahydrofolate reductase gene C677T polymorphism was a risk factor for thrombotic stroke. A multicenter case-control study in China. Stroke 34: 2085–2090.
Linnebank M, Montenarh M, Kölsch H, Linnebank A, Schnez K, Schweichel D, et al. 2005. Common genetic variants of homocysteine metabolism in ischemic stroke: a case-control study. Eur J Neurol 12: 614–618.
Markus HS, Ali N, Swaminathan R, Sankaralingam A, Molloy J, Powell J, 1997. A common polymorphism in the methylenetetrahydrofolate reductase gene, homocysteine, and ischemic cerebrovascular disease. Stroke 28: 1739–1743.
Miller SP, Wu YW, Lee J, Lammer EJ, Iovannisci DM, Glidden DV, et al. 2006. Candidate gene polymorphisms do not differ between newborns with stroke and normal controls. Stroke 37: 2678–2683.
Morita H, Kurihara H, Tsubaki S, Sugiyama T, Hamada C, Kiruhara Y, et al. 1998. Methylenetetrahydrofolate reductase gene polymorphism and ischemic stroke in Japanese. Arterioscl Throm Vas Biol 18: 1465–1469.
Morita H, Taguchi J, Kurihara H, Kitaoka M, Kaneda H, Kurihara Y, et al. 1997. Genetic polymorphism of 5, 10-methylenetetrahydrofolate reductase (MTHFR) as a risk factor for coronary artery disease. Circulation 95: 2032–2036.
Morizane M, Yoshida S, Nakago S, Hamana S, Maruo T, Kennedy S, 2004. No association of endometriosis with glutathione S-transferase M1 and T1 null mutations in a Japanese population. J Soc Gynecol Invest 11: 118–121.
Moskvina V, Holmans P, Schmidt K, Craddock N, 2005. Design of case-controls studies with unscreened controls. Ann Hum Genet 69: 566–576.
Pezzini A, del Zotto E, Archetti S, Negrini R, Bani P, Albertini A, et al. 2002. Plasma homocysteine concentration, C677T MTHFR genotype, and 844ins68bp CBS genotype in young adults with spontaneous cervical artery dissection and atherothrombotic stroke. Stroke 33: 664–669.
Schürks M, Zee R, Buring J, Kurth T, 2008. Interrelationships among theMTHFR 677C>T polymorphism, migraine, and cardiovascular disease. Neurology 71: 505–513.
Soriente L, Coppola A, Madonna P, Cerbone AM, Di Minno G, Orefice G, et al. 1998. Homozygous C677T mutation of the 5, 10-methylenetetrahydrofolate reductase gene and hyperhomocysteinemia in Italian patients with a history of early-onset ischemic stroke. Stroke 29: 869–871.
Szolnoki Z, Havasi V, Bene J, Komlosi K, Szoke D, Somogyvari F, et al. 2005. Endothelial nitric oxide synthase gene interactions and the risk of ischaemic stroke. Acta Neurol Scand 111: 29–33.
Szolnoki Z, Melegh B, 2006. Gene-gene and gene-environment interplay represent specific susceptibility for different types of ischaemic stroke and leukoaraiosis. Curr Med Chem 13: 1627–1634.
Szolnoki Z, Somogyvari F, Kondacs A, Szabo M, Fodor L, Bene J, et al. 2004. Specific APO E genotypes in combination with the ACE D/D or MTHFR 677TT mutation yield an independent genetic risk of leukoaraiosis. Acta Neurol Scand 109: 222–227.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Gorący, I., Cyryłowski, L., Kaczmarczyk, M. et al. C677T polymorphism of the methylenetetrahydrofolate reductase gene and the risk of ischemic stroke in Polish subjects. J Appl Genet 50, 63–67 (2009). https://doi.org/10.1007/BF03195654
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF03195654