Homocysteine, MTHFR 677C→T polymorphism, and risk of ischemic stroke

Kelly, Peter; Rosand, J.; Kistler, J P; Shih, Vivian E.; Silveira, S.; Plomaritoglou, A.; Furie, Karen L.

doi:10.1212/wnl.59.4.529

Cited by 203 publications

(148 citation statements)

References 58 publications

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“…18,19. Similarly, the C667T variant of the MTHFR gene may predict toxicity from methotrexate therapy, and MTHFR gene variants may also be associated with increased risk for several types of cancer, migraine, neural tube defects, and stroke. [20][21][22][23] Several of the variants may provide ancillary risk information about various types of cancer (XRCC1, GSTM1, GSTP1, MTHFR, CYP2C9), many amenable to early detection and surveillance interventions that improve health outcomes. 20,[24][25][26] Based on these findings, we determined that the policy implications of ancillary information would be highly dependent on the characteristics of the individual tests: the strength of the risk estimate, the severity and potential for stigma of the associated disease, and the treatability of the disease.…”

Section: Resultsmentioning

confidence: 99%

Ancillary risk information and pharmacogenetic tests: social and policy implications

2007

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Some pharmacogenetic tests may provide ancillary disease risk information. To evaluate evidence and assess the social and policy implications of ancillary disease risk information associated with candidate pharmacogenetic variants, We conducted a literature search and abstract review of disease susceptibility studies for each of 42 gene variants potentially associated with drug response. Twenty-two variants (53%) had suggested association with disease risk in at least two studies, and sixteen (38%) were for diseases other than the pharmacogenetic indication. Seven variants (16%) were associated with risk for at least two different diseases. Pharmacogenetic tests have the potential to provide ancillary disease risk information, and this potential should be considered as pharmacogenetic tests are brought into clinical use. Implications will vary with each test but tests should be evaluated individually within a framework that outlines the potential implications of ancillary information.

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Section: Resultsmentioning

confidence: 99%

Ancillary risk information and pharmacogenetic tests: social and policy implications

2007

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“…The presence of a homozygous, combined heterozygous, and to a lesser extent, single heterozygous state of the MTHFR polymorphisms might predispose to elevated homocysteine levels, especially when levels of folate, vitamin B6, and/or vitamin B12 are low [12,33]. The resulting hyperhomocysteine is supposed to cause endothelial damage and is associated with an increased risk for arterial and venous thromboembolic events [7,12,19,26]. It also is unclear whether the presence of a heterozygous and especially a homozygous state of MTHFR C677T and/or A1298C polymorphism might result in an increased risk for DVT independently from homocysteine levels.…”

Section: Discussionmentioning

confidence: 99%

Genetic Polymorphisms in Venous Thrombosis and Pulmonary Embolism After Total Hip Arthroplasty: A Pilot Study

Ringwald¹,

Berger²,

Adler³

et al. 2008

Clin Orthop Relat Res

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Deep venous thrombosis (DVT) after major orthopaedic surgery is a substantial concern. We asked whether the single or combined presence of thrombophilic genetic polymorphisms might further increase the already high risk for venous thrombosis and pulmonary embolism (PE) after THA. We therefore compared the prevalence of factor V Leiden, prothrombin G20210A, methylenetetrahydrofolate reductase (MTHFR) C677T and A1298C, and plasminogen activator inhibitor 4G/5G polymorphisms between 50 patients with symptomatic DVT within 3 weeks after elective THA and an asymptomatic control group of 85 patients. We found no major difference for the presence of a single mutation between the groups. Factor V Leiden and homozygous MTHFR C667T mutations were of borderline significance with odds ratios (95% confidence intervals) of 3.73 (0.89-15.63) and 2.93 (0.92-9.29), respectively. Patients with homozygous or combined heterozygous status of MTHFR C677T and A1298C mutation had a higher frequency of DVT after elective THA (odds ratio, 2.86; 95% confidence interval, 1.32-6.35) than those with wild-type.

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“…In a meta-analysis study, Kelly et al 17 analyzed 19 published works (2788 stroke and 3962 nonstroke cases) on MTHFR polymorphism and concluded that the MTHFR 677TT genotype can be considered a mild-to-moderate risk factor for ischemic stroke. These authors found a small influence (pooled OR, 1.23; 95% CI, 0.96-1.58) of the MTHFR 677TT genotype on stroke risk, which showed a trend toward disease, but did not reach the threshold for statistical significance.…”

Section: Discussionmentioning

confidence: 99%

“…15,16 According to Markus et al, 16 the homozygous thermolabile genotype was not associated with ischemic cerebrovascular disease, despite the significant association of the genotype with elevated homocysteine in the patient group. Kelly et al 17 , in another meta-analysis study demonstrated the association between mild-to-moderate hyperhomocysteinemia and ischemic stroke, and more recently this polymorphism has been suggested as a genetic risk factor for ischemic stroke. 18 In contrast, other authors have reported that the MTHFR 677TT genotype may have a small influence in determining susceptibility to ischemic stroke.…”

Section: Introductionmentioning

confidence: 96%

Methylenetetrahydrofolate Reductase Gene Polymorphism Is Not Related to the Risk of Ischemic Cerebrovascular Disease in a Brazilian Population

Shinjo

Oba-Shinjo

Silva

et al. 2007

Clinics

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reductase gene polymorphism is not related to the risk of ischemic cerebrovascular disease in the a Brazilian population. Clinics. 2007;62(3):295-300. PURPOSE:Data are conflicting concerning the risk for ischemic stroke associated with a common polymorphism in the gene encoding 5,10-methylenetetrahydrofolate reductase C677T, which predisposes carriers to hyperhomocysteinemia. A meta-analysis study suggested that the 5,10-methylenetetrahydrofolate reductase 677TT genotype might have a small influence in determining susceptibility to ischemic stroke. METHODS: We analyzed the 5,10-methylenetetrahydrofolate reductase 677TT genotype polymorphism in Brazilian subjects with ischemic stroke, using a case-control design. RESULTS: We compared 5,10-methylenetetrahydrofolate reductase genotypes in groups of subjects presenting ischemic stroke (n = 127) and normal control (n = 126) and found an odds ratio of 1.97 (95% CI, 0.84-4.64) in a multivariate analysis in which results were adjusted to baseline clinical characteristics of study participants. CONCLUSION: We found that the homozygous 5,10-methylenetetrahydrofolate reductase C677T genotype was not a risk factor for ischemic stroke in these Brazilian subjects.

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Homocysteine, MTHFR 677C→T polymorphism, and risk of ischemic stroke

Abstract: These data support an association between mild-to-moderate hyper-Hcy and ischemic stoke. The MTHFR TT genotype may have a small influence in determining susceptibility to ischemic stoke.

Cited by 203 publications

References 58 publications

Ancillary risk information and pharmacogenetic tests: social and policy implications

Ancillary risk information and pharmacogenetic tests: social and policy implications

Genetic Polymorphisms in Venous Thrombosis and Pulmonary Embolism After Total Hip Arthroplasty: A Pilot Study

Methylenetetrahydrofolate Reductase Gene Polymorphism Is Not Related to the Risk of Ischemic Cerebrovascular Disease in a Brazilian Population

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