Simon Cronin1, Karen L Furie, Peter J Kelly. 1. Neurovascular Clinical Science Unit, Mater Misericordiae University Hospital, Eccles St, Dublin 7, Ireland.
Abstract
BACKGROUND: Data are conflicting concerning ischemic stroke risk associated with a common polymorphism in the gene encoding 5,10-methylenetetrahydrofolate reductase (MTHFR 677C-->T), which predisposes to hyperhomocystinemia in vivo. METHODS: We performed a systematic review and meta-analysis of published relevant literature. We included cohort, case-control, or cross-sectional studies reporting the frequencies of heterozygous (CT) and homozygous (TT) genotypes in (a) all stroke/TIA (overall group) and (b) imaging-proven ischemic stroke (best-phenotyped group). RESULTS: Among 14 870 subjects, the pooled estimated risk of stroke/TIA associated with the 677T allele increased in a dose-dependent manner (T allele pooled OR 1.17, 95%CI 1.09 to 1.26, TT genotype pooled OR 1.37, 95%CI 1.15 to 1.64). An almost-identical relationship was observed when the analysis was restricted to imaging-proven ischemic stroke (T allele pooled OR 1.18, 95%CI 1.09 to 1.29, TT genotype pooled OR 1.48, 95%CI 1.22 to 1.8). CONCLUSIONS: A graded increase in ischemic stroke risk with increasing MTHFR 677T allele dose was observed, suggesting an influence of this polymorphism as a genetic stroke risk factor and supporting other evidence indicating a causal relationship between elevated homocysteine and stroke.
BACKGROUND: Data are conflicting concerning ischemic stroke risk associated with a common polymorphism in the gene encoding 5,10-methylenetetrahydrofolate reductase (MTHFR 677C-->T), which predisposes to hyperhomocystinemia in vivo. METHODS: We performed a systematic review and meta-analysis of published relevant literature. We included cohort, case-control, or cross-sectional studies reporting the frequencies of heterozygous (CT) and homozygous (TT) genotypes in (a) all stroke/TIA (overall group) and (b) imaging-proven ischemic stroke (best-phenotyped group). RESULTS: Among 14 870 subjects, the pooled estimated risk of stroke/TIA associated with the 677T allele increased in a dose-dependent manner (T allele pooled OR 1.17, 95%CI 1.09 to 1.26, TT genotype pooled OR 1.37, 95%CI 1.15 to 1.64). An almost-identical relationship was observed when the analysis was restricted to imaging-proven ischemic stroke (T allele pooled OR 1.18, 95%CI 1.09 to 1.29, TT genotype pooled OR 1.48, 95%CI 1.22 to 1.8). CONCLUSIONS: A graded increase in ischemic stroke risk with increasing MTHFR 677T allele dose was observed, suggesting an influence of this polymorphism as a genetic stroke risk factor and supporting other evidence indicating a causal relationship between elevated homocysteine and stroke.
Authors: Susan M Wernimont; Andrew G Clark; Patrick J Stover; Martin T Wells; Augusto A Litonjua; Scott T Weiss; J Michael Gaziano; Pantel S Vokonas; Katherine L Tucker; Patricia A Cassano Journal: J Nutr Date: 2012-05-30 Impact factor: 4.798
Authors: Isabelle R Miousse; Charles M Skinner; Vijayalakshmi Sridharan; John W Seawright; Preeti Singh; Reid D Landes; Amrita K Cheema; Martin Hauer-Jensen; Marjan Boerma; Igor Koturbash Journal: Life Sci Space Res (Amst) Date: 2019-05-31