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ISSN: 1641-4640
Folia Neuropathologica
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vol. 56
Original paper

Correlations between plasma homocysteine and MTHFR gene polymorphism and white matter lesions

Min Li, Bing Fu, Wanli Dong

Folia Neuropathol 2018; 56 (4): 301-307
Online publish date: 2018/12/31
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This study aims to investigate the correlation between the plasma homocysteine (Hcy) level and methylenetetrahydro­folate reductase (MTHFR) C677T polymorphism, and white matter lesions (WML). The plasma Hcy level and MTHFR C677T gene polymorphism in 104 patients with white matter lesions and 74 controls were measured. The severity of cerebral white matter was scored on the magnetic resonance imaging (MRI) images by the modified Scheltens scale (score of 0-30). The plasma Hcy level in the WML group was remarkably higher than that in the control group (p < 0.05), and the proportion of the patients with a high Hcy level in the WML group was notably higher than that in the control group (p < 0.05). Moreover, the patients with TT genotype in MTHFR gene had a significantly higher plasma Hcy level than those with CT or CC genotype. In addition, the plasma Hcy level in the patients with CT genotype was also significantly different from that in the patients with CC genotype (p < 0.05). The severity of cerebral white matter lesions among the patients with different genotypes in MTHFR gene was not significantly different (p > 0.05). The plasma Hcy level is positively correlated with WML and significantly correlated with C677T gene polymorphism in MTHFR gene. The severity of white matter lesions is not correlated with MTHFR C677T gene polymorphism.

brain white matter disease, gene polymorphism, homocysteine, MTHFR, risk factors

Abhinand PA, Manikandan M, Mahalakshmi R, Ragunath PK. Meta-analysis study to evaluate the association of MTHFR C677T polymorphism with risk of ischemic stroke. Bioinformation 2017; 13: 214-219.
Chang YT, Hsu SW, Tsai SJ, Chang YT, Huang CW, Liu ME, Chen NC, Chang WN, Hsu JL, Lee CC, Chang CC. Genetic effect of MTHFR C677T polymorphism on the structural covariance network and white-matter integrity in Alzheimer’s disease. Hum Brain Mapp 2017; 38: 3039-3051.
Cloonan L, Fitzpatrick KM, Kanakis AS, Furie KL, Rosand J, Rost NS. Metabolic determinants of white matter hyperintensity burden in patients with ischemic stroke. Atherosclerosis 2015; 240: 149-153.
de Lau LM, van Meurs JB, Uitterlinden AG, Smith AD, Refsum H, Johnston C, Breteler MM. Genetic variation in homocysteine metabolism, cognition, and white matter lesions. Neurobiol Aging 2010; 31: 2020-2022.
Della-Morte D, Dong C, Markert MS, Elkind MSV, Sacco RL, Wright CB, Rundek T. Carotid Intima-Media Thickness Is Associated With White Matter Hyperintensities: The Northern Manhattan Study. Stroke 2018; 49: 304-311.
Dogru M, Aydin H, Aktas A, Cirik AA. Methylenetetrahydrofolate Reductase gene polymorphism in children with allergic rhinitis. Allergol Immunopathol (Madr) 2015; 43: 579-583.
Feng C, Bai X, Xu Y, Hua T, Huang J, Liu XY. Hyperhomocysteinemia associates with small vessel disease more closely than large vessel disease. Int J Med Sci 2013; 10: 408-412.
Guo T, Chen H, Liu B, Ji W, Yang C. Methylenetetrahydrofolate reductase polymorphisms C677T and risk of autism in the Chinese Han population. Genet Test Mol Biomarkers 2012; 16: 968-973.
Hachinski VC, Potter P, Merskey H. Leuko-araiosis. Arch Neurol 1987; 44: 21-23.
Hainsworth AH, Fisher MJ. A dysfunctional blood-brain barrier and cerebral small vessel disease. Neurology 2017; 88: 420-421.
Hofer E, Cavalieri M, Bis JC, DeCarli C, Fornage M, Sigurdsson S, Srikanth V, Trompet S, Verhaaren BF, Wolf C, Yang Q, Adams HH, Amouyel P, Beiser A, Buckley BM, Callisaya M, Chauhan G, de Craen AJ, Dufouil C, van Duijn CM, Ford I, Freudenberger P, Gottesman RF, Gudnason V, Heiss G, Hofman A, Lumley T, Martinez O, Mazoyer B, Moran C, Niessen WJ, Phan T, Psaty BM, Satizabal CL, Sattar N, Schilling S, Shibata DK, Slagboom PE, Smith A, Stott DJ, Taylor KD, Thomson R, Töglhofer AM, Tzourio C, van Buchem M, Wang J, Westendorp RG, Windham BG, Vernooij MW, Zijdenbos A, Beare R, Debette S, Ikram MA, Jukema JW, Launer LJ, Longstreth WT Jr, Mosley TH, Seshadri S, Schmidt H, Schmidt R; Cohorts for Heart and Aging Research in Genomic Epidemiology Consortium. White Matter Lesion Progression: Genome-Wide Search for Genetic Influences. Stroke 2015; 46: 3048-3057.
Jeon SB, Kang DW, Kim JS, Kwon SU. Homocysteine, small-vessel disease, and atherosclerosis: an MRI study of 825 stroke patients. Neurology 2014; 83: 695-701.
Kloppenborg RP, Geerlings MI, Visseren FL, Mali WP, Vermeulen M, van der Graaf Y, Nederkoorn PJ; SMART Study Group. Homocysteine and progression of generalized small-vessel disease: the SMART-MR Study. Neurology 2014; 82: 777-783.
Li L, Wu SD, Wang JY, Shen XZ, Jiang W. MTHFR polymorphisms and pancreatic cancer risk: lack of evidence from a meta-analysis. Asian Pac J Cancer Prev 2012; 13: 2249-2252.
Nezu T, Hosomi N, Aoki S, Kubo S, Araki M, Mukai T, Takahashi T, Maruyama H, Higashi Y, Matsumoto M. Endothelial dysfunction is associated with the severity of cerebral small vessel disease. Hypertens Res 2015; 38: 291-297.
Pařízková M, Andel R, Lerch O, Marková H, Gažová I, Vyhnálek M, Hort J, Laczó J. Homocysteine and Real-Space Navigation Performance among Non-Demented Older Adults. J Alzheimers Dis 2017; 55: 951-964.
Pavlovic AM, Pekmezovic T, Obrenovic R, Novakovic I, Tomic G, Mijajlovic M, Sternic N. Increased total homocysteine level is associated with clinical status and severity of white matter changes in symptomatic patients with subcortical small vessel disease. Clin Neurol Neurosurg 2011; 113: 711-715.
Poggesi A, Pasi M, Pescini F, Pantoni L, Inzitari D. Circulating biologic markers of endothelial dysfunction in cerebral small vessel disease: A review. J Cereb Blood Flow Metab 2016; 36: 72-94.
Rajagopalan P, Jahanshad N, Stein JL, Hua X, Madsen SK, Kohannim O, Hibar DP, Toga AW, Jack CR Jr, Saykin AJ, Green RC, Weiner MW, Bis JC, Kuller LH, Riverol M, Becker JT, Lopez OL, Thompson PM; Alzheimer’s Disease Neuroimaging Initiative (ADNI); Cardiovascular Health Study (CHS). Common folate gene variant, MTHFR C677T, is associated with brain structure in two independent cohorts of people with mild cognitive impairment. Neuroimage Clin 2012; 1: 179-187.
Rutten-Jacobs LC, Traylor M, Adib-Samii P, Thijs V, Sudlow C, Rothwell PM, Boncoraglio G, Dichgans M, Meschia J, Maguire J, Levi C,
Rost NS, Rosand J, Hassan A, Bevan S, Markus HS. Association of MTHFR C677T Genotype With Ischemic Stroke Is Confined to Cerebral Small Vessel Disease Subtype. Stroke 2016; 47: 646-651.
Scheltens P, Barkhof F, Leys D, Pruvo JP, Nauta JJ, Vermersch P, Steinling M, Valk J. A semiquantative rating scale for the assessment of signal hyperintensities on magnetic resonance imaging. J Neurol Sci 1993; 114: 7-12.
Smith EE. Leukoaraiosis and stroke. Stroke 2010; 41: S139-143.
Tran T, Cotlarciuc I, Yadav S, Hasan N, Bentley P, Levi C, Worrall BB, Meschia JF, Rost N, Sharma P. Candidate-gene analysis of white matter hyperintensities on neuroimaging. J Neurol Neurosurg Psychiatry 2016; 87: 260-266.
Vermeer SE, van Dijk EJ, Koudstaal PJ, Oudkerk M, Hofman A, Clarke R, Breteler MM. Homocysteine, silent brain infarcts, and white matter lesions: The Rotterdam Scan Study. Ann Neurol 2002; 51: 285-289.
Vijayan M, Chinniah R, Ravi PM, Sivanadham R, Mosses Joseph AK, Vellaiappan NA, Krishnan JI, Karuppiah B. MTHFR (C677T) CT genotype and CT-apoE3/3 genotypic combination predisposes the risk of ischemic stroke. Gene 2016; 591: 465-470.
Wang CY, Chen ZW, Zhang T, Liu J, Chen SH, Liu SY, Han LY, Hui ZH, Chen YM. Elevated plasma homocysteine level is associated with ischemic stroke in Chinese hypertension patients. Eur J Intern Med 2014; 25: 538-544.
Yang B, Fan S, Zhi X, Xia R, Wang Y, Zheng Q, Sun G. Geographical and ethnic distribution of MTHFR gene polymorphisms and their associations with diseases among Chinese population. Clin Genet 2017; 92: 243-258.
Yan H, Wu A. FOXO1 is crucial in glioblastoma cell tumorigenesis and regulates the expression of SIRT1 to suppress senescence in the brain. Mol Med Rep 2018; 17: 2535-2542.
Zhang L, Yin RX, Liu WY, Miao L, Wu DF, Aung LH, Hu XJ, Cao XL, Wu JZ, Pan SL. Association of methylenetetrahydrofolate reductase C677T polymorphism and serum lipid levels in the Guangxi Bai Ku Yao and Han populations. Lipids Health Dis 2010; 9: 123.
Zhu Y, Wu T, Ye L, Li G, Zeng Y, Zhang Y. Prevalent genotypes of methylenetetrahydrofolate reductase (MTHFR) in recurrent miscarriage and recurrent implantation failure. J Assist Reprod Genet 2018; 35: 1437-1442.
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