Homozygous C677T Mutation of the 5,10 Methylenetetrahydrofolate Reductase Gene and Hyperhomocysteinemia in Italian Patients With a History of Early-Onset Ischemic Stroke

Soriente, Lucia; Coppola, Antonio; Madonna, Pasquale; Cerbone, Anna Maria; Minno, Giovanni Di; Orefice, G.; D’Angelo, Armando

doi:10.1161/01.str.29.4.869

Cited by 33 publications

(24 citation statements)

References 10 publications

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“…This is consistent with studies conducted in Japanese 15 and Italians. 16 Frosst et al 31 first suggested that the C677T polymorphism in the MTHFR gene was a candidate risk factor for vascular disease. However, subsequent results are controversial.…”

Section: Et Al Homocysteine and Mthfr C677t Polymorphism In Strokementioning

confidence: 99%

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Elevated Plasma Homocysteine Was Associated With Hemorrhagic and Ischemic Stroke, but Methylenetetrahydrofolate Reductase Gene C677T Polymorphism Was a Risk Factor for Thrombotic Stroke

Sun²,

Zhang³

et al. 2003

Stroke

186

139

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Background and Purpose-It is still controversial whether elevated plasma homocysteine and the C677T polymorphism of methylenetetrahydrofolate reductase (MTHFR) gene are risk factors for stroke. The aim of the present study was to investigate the association between the 2 factors and stroke in Chinese in a large case-control study. Methods-We recruited 1823 stroke patients (807 cerebral thrombosis, 513 lacunar infarction, 503 intracerebral hemorrhage) and 1832 controls. Total plasma homocysteine was determined by high-performance liquid chromatography. C677T polymorphism was genotyped by polymerase chain reaction and HinfI digestion. Results-Total plasma homocysteine levels were significantly higher in cases than controls (median, 14.7 versus 12.8 mol/L; PϽ0.001) and associated with an increased risk of 1.87-fold (95% confidence interval [CI], 1.58 to 2.22) for overall stroke, 1.72-fold (95% CI, 1.39 to 2.12) for cerebral thrombosis, 1.89-fold (95% CI, 1.50 to 2.40) for lacunar infarction, and 1.94-fold (95% CI, 1.48 to 2.55) for intracerebral hemorrhage. The C677T mutation of the MTHFR gene was positively correlated with plasma homocysteine levels in both controls (␤ϭ0.250, PϽ0.001) and cases (␤ϭ0.272, PϽ0.001) and more frequently in cases than in controls (47.0% versus 44.2%, Pϭ0.017). The TT genotype was associated with an increased risk for overall stroke (odds ratio, 1.27; 95% CI, 1.04 to 1.56) and thrombotic stroke (odds ratio, 1.37; 95% CI, 1.06 to 1.78). Conclusions-The C677T polymorphism of the MTHFR gene was associated with increased risk of cerebral thrombotic stroke in Chinese. Total plasma homocysteine was correlated with both ischemic and hemorrhagic stroke, suggesting potential initiation of homocysteine-lowering therapy in this population.

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Section: Et Al Homocysteine and Mthfr C677t Polymorphism In Strokementioning

confidence: 99%

“…Polymorphism of MTHFR C677T leads to a reduction in enzyme activity and subsequent elevation of plasma homocysteine. 14 The C677T mutation has been reported to be associated with ischemic stroke in some studies 15,16 but not in others. [17][18][19][20][21][22] Small sample size and various ethnic groups and methodologies might contribute to the discrepancy.…”

mentioning

confidence: 98%

Elevated Plasma Homocysteine Was Associated With Hemorrhagic and Ischemic Stroke, but Methylenetetrahydrofolate Reductase Gene C677T Polymorphism Was a Risk Factor for Thrombotic Stroke

Sun²,

Zhang³

et al. 2003

Stroke

186

139

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“…Case-control and observational studies suggest that patients with sCAD have a mild elevation of total homocysteine (tHcy) levels, an increased prevalence of hyperhomocysteinemia, or both (Benninger et al 2009;Gallai et al 2001;Konrad et al 2004;Pezzini et al 2002). The tHcy levels in patients with sCAD (± ischemic stroke) are lower compared to those in patients with ischemic stroke not due to sCAD (Benninger et al 2009;Kelly et al 2002;Pezzini et al 2002;Soriente et al 1998). Hyperhomocysteinemia damages the endothelium according to in vitro and animal studies (Harker et al 1976;Harker et al 1974;Wall et al 1980), impairs endothelial-dependent and flow mediated vasodilation in humans (Woo et al 1997), and is associated with premature peripheral and cerebrovascular disease and atherosclerosis in case-control studies (Boers et al 1985;Clarke et al 1991).…”

Section: Vascular Risk Factorsmentioning

confidence: 99%

Management of Spontaneous Dissection of the Cervical Carotid Artery

Baumgartner

2009

Surgical Management of Cerebrovascular Disease

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This manuscript reviews the management of patients with spontaneous dissection of the cervical internal carotid artery (sICAD). Recommendations are not based on controlled-randomized trials, but on case-control and observational, hospital-based studies, and case reports. Vascular risk factors seem to be as prevalent in patients with sICAD as in age-matched, healthy volunteers. Stroke prevention includes the treatment of vascular risk factors and the administration of oral aspirin, which may be as effective as anticoagulation. The few available data indicate that most patients with sICAD causing severe stenosis or occlusion, or an aneurysm can be treated conservatively. Patients with sICAD were not excluded in the intravenous controlled-randomized thrombolysis trials with tissue plasminogen activator, but were excluded in the intraarterial controlled-randomized thrombolysis trials. Taking the few published case series and reports on thrombolysis in patients with sICAD into consideration, intravenous thrombolysis may be beneficial, whereas it remains unclear whether intraarterial thrombolysis is useful. This manuscript reviews the management of patients with spontaneous dissection of the cervical internal carotid artery (sICAD). The first part will deal with stroke prevention, in particular the vascular risk factors, antithrombotic therapy, and the treatment of severe stenosis or occlusion, and dissecting aneurysm. The second part will discuss thrombolytic treatment of acute ischemic stroke due to sICAD. Management of Spontaneous Dissection of the Cervical Carotid Artery

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“…Some studies have examined the relationship between elevated homocysteine levels and the risk of ischemic stroke [15][16][17][18][19][20][21]. Homocysteine metabolism depends on nutritional factors and genetics.…”

Section: Homocysteinementioning

confidence: 99%

“…Acquired hyperhomocysteinemia causes include deficiency of vitamin B12, vitamin B6 or folate, renal failure, hyperthyroidism and drugs (methotrexate, theophylline, phenytoin). The most common genetic mutation of hyperhomocysteinemia is a C-to-T substitution at nucleotide 677 (C677T) of the gene of 5,10-methylenetetrahydrofolate reductase (MTHFR) [15,17]. MTHFR is an enzyme involved in folate metabolism which is important in homocysteine remethylation.…”

Section: Homocysteinementioning

confidence: 99%