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Published in: BMC Neurology 1/2020

01-12-2020 | Stroke | Research article

A prospective cohort study of MTHFR C677T gene polymorphism and its influence on the therapeutic effect of homocysteine in stroke patients with hyperhomocysteinemia

Authors: Xiaoxia Du, Lin Xiao, Rong Sun, Kunpeng Li, Lin Liang, Luping Song, Zhizhong Liu

Published in: BMC Neurology | Issue 1/2020

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Abstract

Background

Hyperhomocysteinemia (HHCY) is a risk factor for cardiovascular and cerebrovascular diseases. The C677T 5, 10-methylenetetrahydrofolate reductase (MTHFR) gene polymorphism increases homocysteine (HCY) levels. This study analyzed the relationship between C677T MTHFR polymorphism and the therapeutic effect of lowering HCY in stroke patients with HHCY.

Methods

Baseline data were collected from stroke patients with HHCY for this prospective cohort study. The C677T MTHFR genotype was detected by polymerase chain reaction-restriction fragment length polymorphism and the therapeutic effect to reduce HCY was compared.

Results

Of 200 stroke patients 162 (81.0%) completed follow-up and were evaluated. Most of them responded well to treatment (103 cases, 63.5%), but 59 (36.4%) patients were in the poor efficacy group. There was a significant difference in terms of age (P < 0.001), hypertension (P = 0.041), hyperuricemia (P = 0.042), HCY after treatment (P < 0.001), and MTHFR genotype (P < 0.001) between the poor efficacy and effective groups, with increased frequency of the TT genotype in the poor efficacy group. Logistic regression showed that the T allele was associated with poor efficacy (OR = 0.733, 95%CI: 0.693, 0.862, P < 0.001). In the codominant model the TT genotype was associated with poor outcome (OR = 0.862, 95%CI: 0.767, 0.970, P = 0.017) and this was also the case in the recessive model (OR = 0.585, 95%CI: 0.462, 0.741, P < 0.001) but there was no association between CT and TT in the dominant model.

Conclusions

The T allele and TT genotype of the MTHFR C677T polymorphism was associated with poor HCY reduction treatment efficacy in stroke patients with HHCY.

Trial registration

The registration number of the clinical trial is ChiCTR1800020048​. Registration date: December 12, 2018.
Literature
1.
go back to reference Bejot Y, Daubail B, Giroud M. Epidemiology of stroke and transient ischemic attacks: current knowledge and perspectives. Rev Neurol. 2016;172(1):59–68.PubMedCrossRef Bejot Y, Daubail B, Giroud M. Epidemiology of stroke and transient ischemic attacks: current knowledge and perspectives. Rev Neurol. 2016;172(1):59–68.PubMedCrossRef
2.
go back to reference Uluduz D, Ince B, Bozluolcay M. Stroke patterns, etiology, and prognosis in patients with diabetes mellitus. Neurology. 2005;64(3):581 author reply 581.PubMedCrossRef Uluduz D, Ince B, Bozluolcay M. Stroke patterns, etiology, and prognosis in patients with diabetes mellitus. Neurology. 2005;64(3):581 author reply 581.PubMedCrossRef
3.
go back to reference Uno M, Kitazato KT, Nishi K, Itabe H, Nagahiro S. Raised plasma oxidised LDL in acute cerebral infarction. J Neurol Neurosurg Psychiatry. 2003;74(3):312–6.PubMedPubMedCentralCrossRef Uno M, Kitazato KT, Nishi K, Itabe H, Nagahiro S. Raised plasma oxidised LDL in acute cerebral infarction. J Neurol Neurosurg Psychiatry. 2003;74(3):312–6.PubMedPubMedCentralCrossRef
4.
go back to reference Spence JD. Homocysteine lowering for stroke prevention: Unravelling the complexity of the evidence. Int J Stroke. 2016;11(7):744–7.PubMedCrossRef Spence JD. Homocysteine lowering for stroke prevention: Unravelling the complexity of the evidence. Int J Stroke. 2016;11(7):744–7.PubMedCrossRef
5.
go back to reference Li J, Jiang S, Zhang Y, Tang G, Wang Y, Mao G, Li Z, Xu X, Wang B, Huo Y. H-type hypertension and risk of stroke in chinese adults: a prospective, nested case-control study. J Transl Int Med. 2015;3(4):171–8.PubMedPubMedCentralCrossRef Li J, Jiang S, Zhang Y, Tang G, Wang Y, Mao G, Li Z, Xu X, Wang B, Huo Y. H-type hypertension and risk of stroke in chinese adults: a prospective, nested case-control study. J Transl Int Med. 2015;3(4):171–8.PubMedPubMedCentralCrossRef
6.
go back to reference Bostom AG, Rosenberg IH, Silbershatz H, Jacques PF, Selhub J, D'Agostino RB, Wilson PW, Wolf PA. Nonfasting plasma total homocysteine levels and stroke incidence in elderly persons: the Framingham study. Ann Intern Med. 1999;131(5):352–5.PubMedCrossRef Bostom AG, Rosenberg IH, Silbershatz H, Jacques PF, Selhub J, D'Agostino RB, Wilson PW, Wolf PA. Nonfasting plasma total homocysteine levels and stroke incidence in elderly persons: the Framingham study. Ann Intern Med. 1999;131(5):352–5.PubMedCrossRef
7.
go back to reference Selhub J. The many facets of hyperhomocysteinemia: studies from the Framingham cohorts. J Nutr. 2006;136(6 Suppl):1726S–30S.PubMedCrossRef Selhub J. The many facets of hyperhomocysteinemia: studies from the Framingham cohorts. J Nutr. 2006;136(6 Suppl):1726S–30S.PubMedCrossRef
8.
go back to reference L S, CJZ L, al DXe. Comparison of etiology and risk factors between young and middle-aged and elderly patients with stroke. Chin J Med Guide. 2016;18(1):5–6. L S, CJZ L, al DXe. Comparison of etiology and risk factors between young and middle-aged and elderly patients with stroke. Chin J Med Guide. 2016;18(1):5–6.
9.
go back to reference Li CJ, Du XX, Yang K, Song LP, Li PK, Wang Q, Sun R, Lin XL, Lu HY, Zhang T. Effects of professional rehabilitation training on the recovery of neurological function in young stroke patients. Neural Regen Res. 2016;11(11):1766–72.PubMedPubMedCentralCrossRef Li CJ, Du XX, Yang K, Song LP, Li PK, Wang Q, Sun R, Lin XL, Lu HY, Zhang T. Effects of professional rehabilitation training on the recovery of neurological function in young stroke patients. Neural Regen Res. 2016;11(11):1766–72.PubMedPubMedCentralCrossRef
10.
go back to reference Hankey GJ, Eikelboom JW. Homocysteine and stroke. Lancet. 2007;365(9455):194–6.CrossRef Hankey GJ, Eikelboom JW. Homocysteine and stroke. Lancet. 2007;365(9455):194–6.CrossRef
11.
go back to reference Omrani HQ, Shandiz EE, Qabai M, Chaman R, Fard HA, Qaffarpoor M. Hyperhomocysteinemia, folateo and B12 vitamin in Iranian patients with acute ischemic stroke. ARYA Atherosclerosis. 2011;7(3):97–101.PubMedPubMedCentral Omrani HQ, Shandiz EE, Qabai M, Chaman R, Fard HA, Qaffarpoor M. Hyperhomocysteinemia, folateo and B12 vitamin in Iranian patients with acute ischemic stroke. ARYA Atherosclerosis. 2011;7(3):97–101.PubMedPubMedCentral
12.
go back to reference Parnetti L, Caso V, Santucci A, Corea F, Lanari A, Floridi A, Conte C, Bottiglieri T. Mild hyperhomocysteinemia is a risk-factor in all etiological subtypes of stroke. Neurol Sci. 2004;25(1):13–7.PubMedCrossRef Parnetti L, Caso V, Santucci A, Corea F, Lanari A, Floridi A, Conte C, Bottiglieri T. Mild hyperhomocysteinemia is a risk-factor in all etiological subtypes of stroke. Neurol Sci. 2004;25(1):13–7.PubMedCrossRef
13.
go back to reference Kalita J, Kumar G, Bansal V, Misra UK. Relationship of homocysteine with other risk factors and outcome of ischemic stroke. Clin Neurol Neurosurg. 2009;111(4):364–7.PubMedCrossRef Kalita J, Kumar G, Bansal V, Misra UK. Relationship of homocysteine with other risk factors and outcome of ischemic stroke. Clin Neurol Neurosurg. 2009;111(4):364–7.PubMedCrossRef
14.
go back to reference Dhamija RK, Gaba P, Arora S, Kaintura A, Kumar M, Bhattacharjee J. Homocysteine and lipoprotein (a) correlation in ischemic stroke patients. J Neurol Sci. 2009;281(1–2):64–8.PubMedCrossRef Dhamija RK, Gaba P, Arora S, Kaintura A, Kumar M, Bhattacharjee J. Homocysteine and lipoprotein (a) correlation in ischemic stroke patients. J Neurol Sci. 2009;281(1–2):64–8.PubMedCrossRef
15.
go back to reference Kawamoto R, Kohara K, Oka Y, Tomita H, Tabara Y, Miki T. An association of 5,10-methylenetetrahydrofolate reductase (MTHFR) gene polymorphism and ischemic stroke. J Stroke Cerebrovasc Dis. 2005;14(2):67–74.PubMedCrossRef Kawamoto R, Kohara K, Oka Y, Tomita H, Tabara Y, Miki T. An association of 5,10-methylenetetrahydrofolate reductase (MTHFR) gene polymorphism and ischemic stroke. J Stroke Cerebrovasc Dis. 2005;14(2):67–74.PubMedCrossRef
16.
go back to reference Li Z, Sun L, Zhang H, Liao Y, Wang D, Zhao B, Zhu Z, Zhao J, Ma A, Han Y, et al. 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. 2003;34(9):2085–90.PubMedCrossRef Li Z, Sun L, Zhang H, Liao Y, Wang D, Zhao B, Zhu Z, Zhao J, Ma A, Han Y, et al. 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. 2003;34(9):2085–90.PubMedCrossRef
17.
go back to reference Song Y, Li B, Wang C, Wang P, Gao X, Liu G. Association between 5,10-Methylenetetrahydrofolate Reductase C677T gene polymorphism and risk of ischemic stroke: a meta-analysis. J Stroke Cerebrovasc Dis. 2016;25(3):679–87.PubMedCrossRef Song Y, Li B, Wang C, Wang P, Gao X, Liu G. Association between 5,10-Methylenetetrahydrofolate Reductase C677T gene polymorphism and risk of ischemic stroke: a meta-analysis. J Stroke Cerebrovasc Dis. 2016;25(3):679–87.PubMedCrossRef
18.
go back to reference Sato S, Uehara T, Hayakawa M, Nagatsuka K, Minematsu K, Toyoda K. Intra- and extracranial atherosclerotic disease in acute spontaneous intracerebral hemorrhage. J Neurol Sci. 2013;332(1–2):116–20.PubMedCrossRef Sato S, Uehara T, Hayakawa M, Nagatsuka K, Minematsu K, Toyoda K. Intra- and extracranial atherosclerotic disease in acute spontaneous intracerebral hemorrhage. J Neurol Sci. 2013;332(1–2):116–20.PubMedCrossRef
19.
go back to reference Zhou Z, Liang Y, Qu H, Zhao M, Guo F, Zhao C, Teng W. Plasma homocysteine concentrations and risk of intracerebral hemorrhage: a systematic review and meta-analysis. Sci Rep. 2018;8(1):2568.PubMedPubMedCentralCrossRef Zhou Z, Liang Y, Qu H, Zhao M, Guo F, Zhao C, Teng W. Plasma homocysteine concentrations and risk of intracerebral hemorrhage: a systematic review and meta-analysis. Sci Rep. 2018;8(1):2568.PubMedPubMedCentralCrossRef
20.
21.
go back to reference Brattstrom L, Lindgren A, Israelsson B, Malinow MR, Norrving B, Upson B, Hamfelt A. Hyperhomocysteinaemia in stroke: prevalence, cause, and relationships to type of stroke and stroke risk factors. Eur J Clin Investig. 1992;22(3):214–21.CrossRef Brattstrom L, Lindgren A, Israelsson B, Malinow MR, Norrving B, Upson B, Hamfelt A. Hyperhomocysteinaemia in stroke: prevalence, cause, and relationships to type of stroke and stroke risk factors. Eur J Clin Investig. 1992;22(3):214–21.CrossRef
22.
go back to reference Verhoef P, Stampfer MJ, Buring JE, Gaziano JM, Allen RH, Stabler SP, Reynolds RD, Kok FJ, Hennekens CH, Willett WC. Homocysteine metabolism and risk of myocardial infarction: relation with vitamins B6, B12, and folate. Am J Epidemiol. 1996;143(9):845–59.PubMedCrossRef Verhoef P, Stampfer MJ, Buring JE, Gaziano JM, Allen RH, Stabler SP, Reynolds RD, Kok FJ, Hennekens CH, Willett WC. Homocysteine metabolism and risk of myocardial infarction: relation with vitamins B6, B12, and folate. Am J Epidemiol. 1996;143(9):845–59.PubMedCrossRef
23.
go back to reference Kalita J, Srivastava R, Bansal V, Agarwal S, Misra UK. Methylenetetrahydrofolate reductase gene polymorphism in Indian stroke patients. Neurol India. 2006;54(3):260–3.PubMedCrossRef Kalita J, Srivastava R, Bansal V, Agarwal S, Misra UK. Methylenetetrahydrofolate reductase gene polymorphism in Indian stroke patients. Neurol India. 2006;54(3):260–3.PubMedCrossRef
24.
go back to reference Kumar A, Kumar P, Prasad M, Sagar R, Yadav AK, Pandit AK, Jali VP, Pathak A. Association of C677T polymorphism in the methylenetetrahydrofolate reductase gene (MTHFR gene) with ischemic stroke: a meta-analysis. Neurol Res. 2015;37(7):568–77.PubMedCrossRef Kumar A, Kumar P, Prasad M, Sagar R, Yadav AK, Pandit AK, Jali VP, Pathak A. Association of C677T polymorphism in the methylenetetrahydrofolate reductase gene (MTHFR gene) with ischemic stroke: a meta-analysis. Neurol Res. 2015;37(7):568–77.PubMedCrossRef
25.
go back to reference Banerjee I, Gupta V, Ganesh S. Association of gene polymorphism with genetic susceptibility to stroke in Asian populations: a meta-analysis. J Hum Genet. 2007;52(3):205–19.PubMedCrossRef Banerjee I, Gupta V, Ganesh S. Association of gene polymorphism with genetic susceptibility to stroke in Asian populations: a meta-analysis. J Hum Genet. 2007;52(3):205–19.PubMedCrossRef
26.
go back to reference Harbuzova V, Polonikov OV, Stroi DO, Matlai OI, Ataman Iu O, Sukharieva VA, Ataman OV. Analysis of the effect of N5, N10-methylenetetrahydrofolate reductase gene C(677)-->T polymorphism on the ischemic stroke development in persons with various risk factors. Fiziolohichnyi zhurnal. 2014;60(2):18–24.PubMedCrossRef Harbuzova V, Polonikov OV, Stroi DO, Matlai OI, Ataman Iu O, Sukharieva VA, Ataman OV. Analysis of the effect of N5, N10-methylenetetrahydrofolate reductase gene C(677)-->T polymorphism on the ischemic stroke development in persons with various risk factors. Fiziolohichnyi zhurnal. 2014;60(2):18–24.PubMedCrossRef
27.
go back to reference Lv Q, Lu J, Wu W, Sun H, Zhang J. Association of the methylenetetrahydrofolate reductase gene A1298C polymorphism with stroke risk based on a meta-analysis. Genet Mol Res. 2013;12(4):6882–94.PubMedCrossRef Lv Q, Lu J, Wu W, Sun H, Zhang J. Association of the methylenetetrahydrofolate reductase gene A1298C polymorphism with stroke risk based on a meta-analysis. Genet Mol Res. 2013;12(4):6882–94.PubMedCrossRef
28.
go back to reference Zhu XY, Hou RY, Pan XD, Wang YC, Zhang ZS, Guo RY. Association between the methylenetetrahydrofolate reductase (MTHFR) gene C677T polymorphism and ischemic stroke in the Chinese population: a meta-analysis. Int J Neurosci. 2015;125(12):885–94.PubMedCrossRef Zhu XY, Hou RY, Pan XD, Wang YC, Zhang ZS, Guo RY. Association between the methylenetetrahydrofolate reductase (MTHFR) gene C677T polymorphism and ischemic stroke in the Chinese population: a meta-analysis. Int J Neurosci. 2015;125(12):885–94.PubMedCrossRef
29.
go back to reference Cronin S, Furie KL, Kelly PJ. Dose-related association of MTHFR 677T allele with risk of ischemic stroke: evidence from a cumulative meta-analysis. Stroke. 2005;36(7):1581–7.PubMedCrossRef Cronin S, Furie KL, Kelly PJ. Dose-related association of MTHFR 677T allele with risk of ischemic stroke: evidence from a cumulative meta-analysis. Stroke. 2005;36(7):1581–7.PubMedCrossRef
30.
go back to reference Zhao M, Wang X, He M, Qin X, Tang G, Huo Y, Li J, Fu J, Huang X, Cheng X, et al. Homocysteine and stroke risk: modifying effect of Methylenetetrahydrofolate Reductase C677T polymorphism and folic acid intervention. Stroke. 2017;48(5):1183–90.PubMedCrossRef Zhao M, Wang X, He M, Qin X, Tang G, Huo Y, Li J, Fu J, Huang X, Cheng X, et al. Homocysteine and stroke risk: modifying effect of Methylenetetrahydrofolate Reductase C677T polymorphism and folic acid intervention. Stroke. 2017;48(5):1183–90.PubMedCrossRef
31.
go back to reference The 2010 Guidelines for the diagnosis and treatment of acute ischemic stroke in China. Chinese J Clinic. 2011;39(3):227–233. The 2010 Guidelines for the diagnosis and treatment of acute ischemic stroke in China. Chinese J Clinic. 2011;39(3):227–233.
32.
go back to reference Wang X. Essentials for diagnosis of various cerebrovascular diseases. Chin J Neurol. 1997;3(1):3–4. Wang X. Essentials for diagnosis of various cerebrovascular diseases. Chin J Neurol. 1997;3(1):3–4.
33.
go back to reference Bhargava S, Parakh R, Srivastava LM. Studies on homocysteine demonstrating its significance as a possible tool for differential diagnosis in occlusive vascular disease. Ind J Clin Biochem. 2004;19(1):76–8.CrossRef Bhargava S, Parakh R, Srivastava LM. Studies on homocysteine demonstrating its significance as a possible tool for differential diagnosis in occlusive vascular disease. Ind J Clin Biochem. 2004;19(1):76–8.CrossRef
34.
go back to reference Shen H, Xu Y, Zheng Y, Qian Y, Yu R, Qin Y, Wang X, Spitz MR, Wei Q. Polymorphisms of 5,10-methylenetetrahydrofolate reductase and risk of gastric cancer in a Chinese population: a case-control study. Int J Cancer. 2001;95(5):332–6.PubMedCrossRef Shen H, Xu Y, Zheng Y, Qian Y, Yu R, Qin Y, Wang X, Spitz MR, Wei Q. Polymorphisms of 5,10-methylenetetrahydrofolate reductase and risk of gastric cancer in a Chinese population: a case-control study. Int J Cancer. 2001;95(5):332–6.PubMedCrossRef
35.
go back to reference Schneider JA, Rees DC, Liu YT, Clegg JB. Worldwide distribution of a common methylenetetrahydrofolate reductase mutation. Am J Hum Genet. 1998;62(5):1258–60.PubMedPubMedCentralCrossRef Schneider JA, Rees DC, Liu YT, Clegg JB. Worldwide distribution of a common methylenetetrahydrofolate reductase mutation. Am J Hum Genet. 1998;62(5):1258–60.PubMedPubMedCentralCrossRef
36.
go back to reference Franco RF, Araujo AG, Guerreiro JF, Elion J, Zago MA. Analysis of the 677 C-->T mutation of the methylenetetrahydrofolate reductase gene in different ethnic groups. Thromb Haemost. 1998;79(1):119–21.PubMedCrossRef Franco RF, Araujo AG, Guerreiro JF, Elion J, Zago MA. Analysis of the 677 C-->T mutation of the methylenetetrahydrofolate reductase gene in different ethnic groups. Thromb Haemost. 1998;79(1):119–21.PubMedCrossRef
37.
go back to reference Baum L, Wong KS, Ng HK, Tomlinson B, Rainer TH, Chan DK, Thomas GN, Chen X, Poon P, Cheung WS, et al. Methylenetetrahydrofolate reductase gene A222V polymorphism and risk of ischemic stroke. Clin Chem Lab Med. 2004;42(12):1370–6.PubMedCrossRef Baum L, Wong KS, Ng HK, Tomlinson B, Rainer TH, Chan DK, Thomas GN, Chen X, Poon P, Cheung WS, et al. Methylenetetrahydrofolate reductase gene A222V polymorphism and risk of ischemic stroke. Clin Chem Lab Med. 2004;42(12):1370–6.PubMedCrossRef
38.
go back to reference Goracy I, Cyrylowski L, Kaczmarczyk M, Fabian A, Koziarska D, Goracy J, Ciechanowicz A. C677T polymorphism of the methylenetetrahydrofolate reductase gene and the risk of ischemic stroke in polish subjects. J Appl Genet. 2009;50(1):63–7.PubMedCrossRef Goracy I, Cyrylowski L, Kaczmarczyk M, Fabian A, Koziarska D, Goracy J, Ciechanowicz A. C677T polymorphism of the methylenetetrahydrofolate reductase gene and the risk of ischemic stroke in polish subjects. J Appl Genet. 2009;50(1):63–7.PubMedCrossRef
39.
go back to reference Moe KT, Woon FP, De Silva DA, Wong P, Koh TH, Kingwell B, Chin-Dusting J, Wong MC. Association of acute ischemic stroke with the MTHFR C677T polymorphism but not with NOS3 gene polymorphisms in a Singapore population. Eur J Neurol. 2008;15(12):1309–14.PubMedCrossRef Moe KT, Woon FP, De Silva DA, Wong P, Koh TH, Kingwell B, Chin-Dusting J, Wong MC. Association of acute ischemic stroke with the MTHFR C677T polymorphism but not with NOS3 gene polymorphisms in a Singapore population. Eur J Neurol. 2008;15(12):1309–14.PubMedCrossRef
40.
go back to reference Ubbink JB, Vermaak WJ, van der Merwe A, Becker PJ. Vitamin B-12, vitamin B-6, and folate nutritional status in men with hyperhomocysteinemia. Am J Clin Nutr. 1993;57(1):47–53.PubMedCrossRef Ubbink JB, Vermaak WJ, van der Merwe A, Becker PJ. Vitamin B-12, vitamin B-6, and folate nutritional status in men with hyperhomocysteinemia. Am J Clin Nutr. 1993;57(1):47–53.PubMedCrossRef
41.
go back to reference Meschia JF, Bushnell C, Boden-Albala B, Braun LT, Bravata DM, Chaturvedi S, Creager MA, Eckel RH, Elkind MS, Fornage M, et al. Guidelines for the primary prevention of stroke: a statement for healthcare professionals from the American Heart Association/American Stroke Association. Stroke. 2014;45(12):3754–832.PubMedPubMedCentralCrossRef Meschia JF, Bushnell C, Boden-Albala B, Braun LT, Bravata DM, Chaturvedi S, Creager MA, Eckel RH, Elkind MS, Fornage M, et al. Guidelines for the primary prevention of stroke: a statement for healthcare professionals from the American Heart Association/American Stroke Association. Stroke. 2014;45(12):3754–832.PubMedPubMedCentralCrossRef
42.
go back to reference Saposnik G, Ray JG, Sheridan P, McQueen M, Lonn E. Heart outcomes prevention evaluation I: Homocysteine-lowering therapy and stroke risk, severity, and disability: additional findings from the HOPE 2 trial. Stroke. 2009;40(4):1365–72.PubMedCrossRef Saposnik G, Ray JG, Sheridan P, McQueen M, Lonn E. Heart outcomes prevention evaluation I: Homocysteine-lowering therapy and stroke risk, severity, and disability: additional findings from the HOPE 2 trial. Stroke. 2009;40(4):1365–72.PubMedCrossRef
43.
go back to reference Ji Y, Tan S, Xu Y, Chandra A, Shi C, Song B, Qin J, Gao Y. Vitamin B supplementation, homocysteine levels, and the risk of cerebrovascular disease: a meta-analysis. Neurology. 2013;81(15):1298–307.PubMedCrossRef Ji Y, Tan S, Xu Y, Chandra A, Shi C, Song B, Qin J, Gao Y. Vitamin B supplementation, homocysteine levels, and the risk of cerebrovascular disease: a meta-analysis. Neurology. 2013;81(15):1298–307.PubMedCrossRef
44.
go back to reference Jacques PF, Selhub J, Bostom AG, Wilson PW, Rosenberg IH. The effect of folic acid fortification on plasma folate and total homocysteine concentrations. N Engl J Med. 1999;340(19):1449–54.PubMedCrossRef Jacques PF, Selhub J, Bostom AG, Wilson PW, Rosenberg IH. The effect of folic acid fortification on plasma folate and total homocysteine concentrations. N Engl J Med. 1999;340(19):1449–54.PubMedCrossRef
45.
go back to reference Goldstein LB, Bushnell CD, Adams RJ, Appel LJ, Braun LT, Chaturvedi S, Creager MA, Culebras A, Eckel RH, Hart RG, et al. Guidelines for the primary prevention of stroke: a guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke. 2011;42(2):517–84.PubMedCrossRef Goldstein LB, Bushnell CD, Adams RJ, Appel LJ, Braun LT, Chaturvedi S, Creager MA, Culebras A, Eckel RH, Hart RG, et al. Guidelines for the primary prevention of stroke: a guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke. 2011;42(2):517–84.PubMedCrossRef
46.
go back to reference Sacco RL, Adams R, Albers G, Alberts MJ, Benavente O, Furie K, Goldstein LB, Gorelick P, Halperin J, Harbaugh R. Guidelines for Prevention of Stroke in Patients With Ischemic Stroke or Transient Ischemic Attack: A Statement for Healthcare Professionals From the American Heart Association/American Stroke Association Council on Stroke: Co-Sponsored by the Council on Cardiovascular Radiology and Intervention: the American Academy of Neurology affirms the value of this guideline. Stroke. 2006;37(2):577–617.PubMedCrossRef Sacco RL, Adams R, Albers G, Alberts MJ, Benavente O, Furie K, Goldstein LB, Gorelick P, Halperin J, Harbaugh R. Guidelines for Prevention of Stroke in Patients With Ischemic Stroke or Transient Ischemic Attack: A Statement for Healthcare Professionals From the American Heart Association/American Stroke Association Council on Stroke: Co-Sponsored by the Council on Cardiovascular Radiology and Intervention: the American Academy of Neurology affirms the value of this guideline. Stroke. 2006;37(2):577–617.PubMedCrossRef
47.
go back to reference Kang SS, Wong PW, Bock HG, Horwitz A, Grix A. Intermediate hyperhomocysteinemia resulting from compound heterozygosity of methylenetetrahydrofolate reductase mutations. Am J Hum Genet. 1991;48(3):546–51.PubMedPubMedCentral Kang SS, Wong PW, Bock HG, Horwitz A, Grix A. Intermediate hyperhomocysteinemia resulting from compound heterozygosity of methylenetetrahydrofolate reductase mutations. Am J Hum Genet. 1991;48(3):546–51.PubMedPubMedCentral
48.
go back to reference Cybulska B, Klosiewicz-Latoszek L. Homocysteine--is it still an important risk factor for cardiovascular disease? Kardiol Pol. 2015;73(11):1092–6.PubMedCrossRef Cybulska B, Klosiewicz-Latoszek L. Homocysteine--is it still an important risk factor for cardiovascular disease? Kardiol Pol. 2015;73(11):1092–6.PubMedCrossRef
49.
go back to reference Towfighi A, Markovic D, Ovbiagele B. Pronounced association of elevated serum homocysteine with stroke in subgroups of individuals: a nationwide study. J Neurol Sci. 2010;298(1–2):153–7.PubMedCrossRef Towfighi A, Markovic D, Ovbiagele B. Pronounced association of elevated serum homocysteine with stroke in subgroups of individuals: a nationwide study. J Neurol Sci. 2010;298(1–2):153–7.PubMedCrossRef
Metadata
Title
A prospective cohort study of MTHFR C677T gene polymorphism and its influence on the therapeutic effect of homocysteine in stroke patients with hyperhomocysteinemia
Authors
Xiaoxia Du
Lin Xiao
Rong Sun
Kunpeng Li
Lin Liang
Luping Song
Zhizhong Liu
Publication date
01-12-2020
Publisher
BioMed Central
Keywords
Stroke
Folic Acid
Published in
BMC Neurology / Issue 1/2020
Electronic ISSN: 1471-2377
DOI
https://doi.org/10.1186/s12883-020-01701-8

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