The T Allele of the 677C>T Polymorphism of Methylenetetrahydrofolate Reductase Gene is Associated With an Increased Risk of Ischemic Stroke in Polish Children
Restricted accessOtherFirst published online October, 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
Ischemic stroke is a very rare and multifactorial disease in children. The aim of the study was to analyze the relationship between the methylenetetrahydrofolate reductase (MTHFR) 677C>T polymorphism and stroke in Polish children and to observe whether there is any significant transmission of MTHFR alleles from heterozygous parents to their affected offspring. We analyzed 64 patients with stroke, 122 parents, and 59 healthy children. The MTHFR polymorphism was genotyped using polymerase chain reaction (PCR)-restriction fragment length polymorphism. The T allele was more frequent in the stroke group (38%) than in controls (25%, P = .029, odds ratio = 1.84). We also found higher frequency of T allele in male patients compared to male controls (46% vs. 25%, P = .009, odds ratio = 2.53). The number of T allele carriers was again more prevalent in boys with stroke (71%) than in healthy boys (45%, P = .023, odds ratio = 3.09). The T allele was significantly transmitted in male patients (P < .019). We conclude that the MTHFR 677C>T polymorphism may be considered as a genetic risk factor of childhood stroke, especially in boys.
Broderick J. , Talbot GT, Prenger E., Leach A., Brott T.Stroke in children within a major metropolitan area: the surprising importance of intracerebral hemorrhage. J Child Neurol. 1993;8(3): 250-255.
2.
Chung B., Wong V.Pediatric stroke among Hong Kong Chinese subjects. Pediatrics . 2004;114(2):e206-e212.
3.
Jakubowski H.Protein N-homocysteinylation: implications for atherosclerosis. Biomed Pharmacother. 2001 ;55(8):443-447.
4.
Brattstrom L. , Wilcken DE, Ohrvik J., Brudin L.Common methylenetetrahydrofolate reductase gene mutation leads to hyperhomocysteinemia but not to vascular disease: the result of a meta-analysis. Circulation. 1998 ;98(23):2520-2526.
5.
Refsum H., Ueland PM, Nygård O., Vollset SEHomocysteine and cardiovascular disease. Annu Rev Med. 1998;49:31-62.
6.
Cardo E., Vilaseca MA, Campistol J., Artuch R., Colomé C., Pineda M.Evaluation of hyperhomocysteinaemia in children with stroke. Eur J Paediatr Neurol. 1999;3(3):113-117.
7.
van Beynum IM , Smeitink JA, den Heijer M., te Poele Pothoff MT, Blom HJHyperhomocysteinemia: a risk factor for ischemic stroke in children. Circulation . 1999;99(16):2070-2072.
8.
Sirachainan N. , Tapanapruksakul P., Visudtibhan A., et al. Homocysteine, MTHFR C677 T, vitamin B12, and folate levels in Thai children with ischemic stroke: a case-control study. J Pediatr Hematol Oncol. 2006;28(12):803-808.
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 . 1995;10(1):111-113.
10.
World Health Organization.International Classification of Impairments, Disabilities, and Handicaps. Geneva, Switzerland: World Health Organization; 1980.
11.
Bamford J., Dennis M., Sandercock M., Burn J., Warlow C.The frequency, causes and timing of death within 30 days of the first stroke: the Oxfordshire Community Stroke Project. J Neurol Neurosurg Psychiatry. 1990;53(10):824-829.
12.
Bamford J., Sandercock P., Dennis M., Burn J., Warlow C.Classification and natural history of clinically identifiable subtypes of cerebral infarction. Lancet. 1991;337(8756):1521-1526.
13.
Friedewald WT, Levy RI, Fredrickson DSEstimation of the concentration of low-density lipoprotein cholesterol in plasma, without the use of preparative centrifuge . Clin Chem. 1972;18(6):499-502.
14.
Spielman RS , McGinnis RE, Ewens WJTransmission test for linkage disequilibrium: the insulin gene region and insulin-dependent diabetes mellitus (IDDM). Am J Hum Genet. 1993;52(3):506-516.
15.
Cardo E., Monrós E., Colomé C., et al. Children with stroke: polymorphism of the MTHFR gene, mild hyperhomocysteinemia, and vitamin status. J Child Neurol. 2000;15:295-298.
16.
Rook JL, Nugent DJ, Young G.Pediatric stroke and methylenetetrahydrofolate reductase polymorphisms: an examination of C677T and A1298C mutations. J Pediatr Hematol Oncol. 2005;27(11):590-593.
17.
Nowak-Göttl U., Sträter R., Heinecke A., et al. Lipoprotein (a) and genetic polymorphisms of clotting factor V, prothrombin, and methylenetetrahydrofolate reductase are risk factors of spontaneous ischemic stroke in childhood. Blood. 1999;94(11):3678-3682.
18.
Akar N., Akar E., Deda G., Sipahi T., Orsal A.Factor V.1691 G-A, prothrombin 20210 G-A, and methylenetetrahydrofolate reductase 677 C-T variants in Turkish children with cerebral infarct. J Child Neurol. 1999;14(11):749-751.
19.
Akar N., Akar E., Ozel D., Deda G., Sipahi T.Common mutations at the homocysteine metabolism pathway and pediatric stroke . Thromb Res. 2001;102(2):115-120.
20.
Komitopoulou A., Platokouki H., Kapsimali Z., Pergantou H., Adamtziki E., Aronis S.Mutations and polymorphisms in genes affecting hemostasis proteins and homocysteine metabolism in children with arterial ischemic stroke. Cerebrovasc Dis. 2006;22(1):13-20.
21.
Goracy I., Goracy J., Suliga M., Ciechanowicz A.C677T gene polymorphism of methylenetetrahydrofolate reductase (MTHFR) in patients with myocardial infarction. Pol Arch Med Wewn. 1999;102(4):849-854.
22.
Zak I., Niemiec P., Sarecka B., et al. Carrier-state of D allele in ACE gene insertion/deletion polymorphism is associated with coronary artery disease, in contrast to the C677->T transition in the MTHFR gene. Acta Biochim Pol. 2003;50(2): 527-534.
23.
Sarecka-Hujar B., Zak I., Krauze J.Carrier-state of two or three polymorphic variants of MTHFR, IL-6 and ICAM1 genes increases the risk of coronary artery disease. Kardiol Pol. 2008;66(12):1269-1277.
24.
Zak I., Sarecka B., Balcerzyk A., et al. Methylenetetrahydrofolate reductase gene HinfI 677C->T polymorphism and brain ischemic stroke in children: association pilot-study . Part two. Neurol Dziec. 2004;13(26):31-36.
