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Child's Nervous System

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01-10-2014 | Original Paper

The roles of methylenetetrahydrofolate reductase 677C>T and 1298A>C polymorphisms in moyamoya disease patients

Authors: Young Seok Park, Young Joo Jeon, Hyun Seok Kim, In Bo Han, Joong-Uhn Choi, Dong-Seok Kim, Nam Keun Kim

Published in: Child's Nervous System | Issue 10/2014

Abstract

Purpose

The methylenetetrahydrofolate reductase (MTHFR) 677C>T and 1298A>C polymorphisms, which are associated with hyperhomocysteinemia and nitric oxide (NO) deficiency (which is related to atherothrombosis and cerebral ischemia), have not been studied in moyamoya disease. A case-control study was performed to investigate whether the MTHFR 677C>T and 1298A>C polymorphisms contribute to moyamoya disease (MMD).

Methods

One hundred and seven Korean patients with MMD (mean age, 20.85 ± 15.89 years; 66.4 % female) and 232 healthy control subjects (mean age, 23.99 ± 16.16 years; 56.8 % female) were included. Genotyping for the MTHFR 677C>T and 1298A>C polymorphisms and measurements of homocysteine, folate, vitamin B₁₂, and NO in the cerebrospinal fluid (CSF) were performed. The statistical analysis was performed by multivariate linear regression and logistic regression.

Result

The MTHFR 677CT+TT genotype frequency was significantly increased with early-onset MMD (<10 years) compared with late-onset MMD (≥10 years) (adjusted odds ratio, 3.392; 95 % confidence interval, 1.294–8.893, P = 0.013). The MTHFR 677C-1298C/677T-1298A diplotype (1.71 ± 1.23 arbitrary units) presented significantly lower NO levels in the CSF compared with the 677C-1298A/677C-1298A diplotype (11.40 ± 12.24 arbitrary units).

Conclusion

The MTHFR 677C>T and 1298A>C polymorphisms have restricted roles in the Korean MMD population. Therefore, further studies involving larger and more heterogeneous cohorts are needed to extend our understanding of the influence of polymorphisms in MTHFR and other thrombophilic genes on MMD.

Miyamoto S, Kikuchi H, Karasawa J, Nagata I, Ikota T, Takeuchi S (1984) Study of the posterior circulation in moyamoya disease. Clinical and neuroradiological evaluation. J Neurosurg 61:1032–1037PubMedCrossRef

Kuroda S, Houkin K (2008) Moyamoya disease: current concepts and future perspectives. Lancet Neurol 7:1056–1066PubMedCrossRef

Ikeda H, Sasaki T, Yoshimoto T, Fukui M, Arinami T (1999) Mapping of a familial moyamoya disease gene to chromosome 3p24.2-p26. Am J Hum Genet 64:533–537PubMedCrossRefPubMedCentral

Nanba R, Tada M, Kuroda S, Houkin K, Iwasaki Y (2005) Sequence analysis and bioinformatics analysis of chromosome 17q25 in familial moyamoya disease. Childs Nerv Syst 21:62–68PubMedCrossRef

Inoue TK, Ikezaki K, Sasazuki T, Matsushima T, Fukui M (2000) Linkage analysis of moyamoya disease on chromosome 6. J Child Neurol 15:179–182PubMedCrossRef

Han H, Pyo CW, Yoo DS, Huh PW, Cho KS, Kim DS (2003) Associations of moyamoya patients with HLA class I and class II alleles in the Korean population. J Korean Med Sci 18:876–880PubMedPubMedCentral

Sakurai K, Horiuchi Y, Ikeda H, Ikezaki K, Yoshimoto T, Fukui M, Arinami T (2004) A novel susceptibility locus for moyamoya disease on chromosome 8q23. J Hum Genet 49:278–281PubMedCrossRef

Kang HS, Kim SK, Cho BK, Kim YY, Hwang YS, Wang KC (2006) Single nucleotide polymorphisms of tissue inhibitor of metalloproteinase genes in familial moyamoya disease. Neurosurgery 58:1074–1080PubMedCrossRef

Andreone V, Ciarmiello A, Fusco C, Ambrosanio G, Florio C, Linfante I (1999) Moyamoya disease in Italian monozygotic twins. Neurology 53:1332–1335PubMedCrossRef

10.

Skardoutsou A, Voudris KA, Mastroyianni S, Vagiakou E, Magoufis G, Koukoutsakis P (2007) Moyamoya syndrome in a child with pyruvate kinase deficiency and combined prothrombotic factors. J Child Neurol 22:474–478PubMedCrossRef

11.

Arruda VR, von Zuben PM, Chiaparini LC, Annichino-Bizzacchi JM, Costa FF (1997) The mutation Ala677-->Val in the methylene tetrahydrofolate reductase gene: a risk factor for arterial disease and venous thrombosis. Thromb Haemost 77:818–821PubMed

12.

Lossos A, Teltsh O, Milman T, Meiner V, Rozen R, Leclerc D, Schwahn BC, Karp N, Rosenblatt DS, Watkins D, Shaag A, Korman SH, Heyman SN, Gal A, Newman JP, Steiner-Birmanns B, Abramsky O, Kohn Y (in press) Severe methylenetetrahydrofolate reductase deficiency: clinical clues to a potentially treatable cause of adult-onset hereditary spastic paraplegia. JAMA Neurol PMID:24797679

13.

Lemarié CA, Shbat L, Marchesi C, Angulo OJ, Deschênes ME, Blostein MD, Paradis P, Schiffrin EL (2011) Mthfr deficiency induces endothelial progenitor cell senescence via uncoupling of eNOS and downregulation of SIRT1. Am J Physiol Heart Circ Physiol 300:H745–753PubMedCrossRef

14.

Signorello M, Viviani GL, Armani U, Cerone R, Minniti G, Piana A, Leoncini G (2007) Homocysteine, reactive oxygen species and nitric oxide in type 2 diabetes mellitus. Thromb Res 120:607–613PubMedCrossRef

15.

Kang SS, Zhou J, Wong PW, Kowalisyn J, Strokosch G (1988) Intermediate homocysteinemia: a thermolabile variant of methylenetetrahydrofolate reductase. Am J Hum Genet 43:414–421PubMedPubMedCentral

16.

Frosst P, Blom HJ, Milos R, Goyette P, Sheppard CA, Matthews RG, Boers GJ, den Heijer M, Kluijtmans LA, van den Heuvel LP, Rozen R (1995) A candidate genetic risk factor for vascular disease: a common mutation in methylenetetrahydrofolate reductase. Nat Genet 10:111–113PubMedCrossRef

17.

Ueland PM, Hustad S, Schneede J, Refsum H, Vollset SE (2001) Biological and clinical implications of the MTHFR C677T polymorphism. Trends Pharmacol Sci 22:195–201PubMedCrossRef

18.

van der Put NM, Gabreëls F, Stevens EM, Smeitink JA, Trijbels FJ, Eskes TK, van den Heuvel LP, Blom HJ (1998) A second common mutation in the methylenetetrahydrofolate reductase gene: an additional risk factor for neural-tube defects? Am J Hum Genet 62:1044–1051PubMedCrossRefPubMedCentral

19.

Weisberg I, Tran P, Christensen B, Sibani S, Rozen R (1998) A second genetic polymorphism in methylenetetrahydrofolate reductase (MTHFR) associated with decreased enzyme activity. Mol Genet Metab 64(3):169–172PubMedCrossRef

20.

Gellekink H, den Heijer M, Heil SG, Blom HJ (2005) Genetic determinants of plasma total homocysteine. Semin Vasc Med 5:98–109PubMedCrossRef

21.

Weisberg IS, Jacques PF, Selhub J, Bostom AG, Chen Z, Curtis Ellison R, Eckfeldt JH, Rozen R (2001) The 1298A-->C polymorphism in methylenetetrahydrofolate reductase (MTHFR): in vitro expression and association with homocysteine. Atherosclerosis 156:409–415PubMedCrossRef

22.

Matsushima T, Inoue T, Suzuki SO, Fujii K, Fukui M, Hasuo K (1992) Surgical treatment of moyamoya disease in pediatric patients—comparison between the results of indirect and direct revascularization procedures. Neurosurgery 31:401–405PubMedCrossRef

23.

Griess P (1879) Bemerkungen zu der abhandlung der HH Weselsky und Benedikt. “Ueber einige azoverbindungen”. Chem Ber 12:426–428CrossRef

24.

Green LC, Wagner DA, Glogowski J, Skipper PL, Wishnok JS, Tannenbaum SR (1982) Analysis of nitrate, nitrite, and [15N]nitrate in biological fluids. Anal Biochem 126:131–138PubMedCrossRef

25.

Cho HJ, Jung YH, Kim YD, Nam HS, Kim DS, Heo JH (2011) The different infarct patterns between adulthood-onset and childhood-onset moyamoya disease. J Neurol Neurosurg Psychiatry 82:38–40PubMedCrossRef

26.

Kastrup A, Schulz JB, Mader I, Dichgans J, Küker W (2002) Diffusion-weighted MRI in patients with symptomatic internal carotid artery disease. J Neurol 249:1168–1174PubMedCrossRef

27.

Bonduel M, Hepner M, Sciuccati G, Torres AF, Tenembaum S (2001) Prothrombotic disorders in children with moyamoya syndrome. Stroke 32:1786–1792PubMedCrossRef

28.

Horn P, Bueltmann E, Buch CV, Schmiedek P (2005) Arterio-embolic ischemic stroke in children with moyamoya disease. Child Nerv Syst 21:104–107CrossRef

29.

Yamashita M, Oka K, Tanaka K (1983) Histopathology of the brain vascular network in moyamoya disease. Stroke 14:50–58PubMedCrossRef

30.

Moro MA, Cárdenas A, Hurtado O, Leza JC, Lizasoain I (2004) Role of nitric oxide after brain ischaemia. Cell Calcium 36:265–275PubMedCrossRef

31.

Blanco S, Castro L, Hernández R, Del Moral ML, Pedrosa JA, Martínez-Lara E, Siles E, Peinado MA (2007) Age modulates the nitric oxide system response in the ischemic cerebellum. Brain Res 1157:66–73PubMedCrossRef

32.

Ruel M, Khan TA, Voisine P, Bianchi C, Sellke FW (2004) Vasomotor dysfunction after cardiac surgery. Eur J Cardiothorac Surg 26:1002–1014PubMedCrossRef

33.

Moncada S, Higgs A (1993) The l-arginine-nitric oxide pathway. N Engl J Med 329:2002–2012PubMedCrossRef

34.

Noda A, Suzuki Y, Takayasu M, Watanabe K, Takagi T, Hara M, Yoshida J (2000) Elevation of nitric oxide metabolites in the cerebrospinal fluid of patients with moyamoya disease. Acta Neurochir 142:1275–1279PubMedCrossRef

35.

Charriaut-Marlangue C, Nguyen T, Bonnin P, Duy AP, Leger PL, Csaba Z, Pansiot J, Bourgeois T, Renolleau S, Baud O (2014) Sildenafil mediates blood-flow redistribution and neuroprotection after neonatal hypoxia-ischemia. Stroke 45:850–856PubMedCrossRef

Title: The roles of methylenetetrahydrofolate reductase 677C>T and 1298A>C polymorphisms in moyamoya disease patients
Authors: Young Seok Park
Young Joo Jeon
Hyun Seok Kim
In Bo Han
Joong-Uhn Choi
Dong-Seok Kim
Nam Keun Kim
Publication date: 01-10-2014
Publisher: Springer Berlin Heidelberg
Published in: Child's Nervous System / Issue 10/2014
Print ISSN: 0256-7040
Electronic ISSN: 1433-0350
DOI: https://doi.org/10.1007/s00381-014-2495-3

Keynote webinar | Spotlight on medication adherence

Springer Medicine

The roles of methylenetetrahydrofolate reductase 677C>T and 1298A>C polymorphisms in moyamoya disease patients

Abstract

Purpose

Methods

Result

Conclusion

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Purpose

Methods

Result

Conclusion

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