Published online before print June 9, 2005, doi: 10.1161/01.STR.0000169946.31639.af
(Stroke. 2005;36:1581.)
© 2005 American Heart Association, Inc.
Comments, Opinions, and Reviews |
Dose-Related Association of MTHFR 677T Allele With Risk of Ischemic Stroke
Evidence From a Cumulative Meta-Analysis
From the Neurovascular Clinical Science Unit (S.C., P.J.K.), Department of Neurology, Mater Misericordiae University Hospital, Dublin, Ireland; and the Stroke Service (K.L.F., P.J.K.), Department of Neurology, Massachusetts General Hospital, Boston.
Correspondence to Dr Peter J. Kelly, Consultant Neurologist, Neurovascular Clinical Science Unit, Mater Misericordiae University Hospital, Eccles St, Dublin 7, Ireland. E-mail pjkelly{at}partners.org
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).
Conclusion— 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.
Key Words: cerebrovascular disorders • folic acid • gene mutation • homocysteine
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