Effect modification by population dietary folate on the association between MTHFR genotype, homocysteine, and stroke risk: a meta-analysis of genetic studies and randomised trials

Michael V Holmes, Paul Newcombe, Jaroslav A Hubacek, Reecha Sofat, Sally L Ricketts, Jackie Cooper, Monique M B Breteler, Leonelo E Bautista, Pankaj Sharma, John C Whittaker, Liam Smeeth, F Gerald R Fowkes, Ale Algra, Veronika Shmeleva, Zoltan Szolnoki, Mark Roest, Michael Linnebank, Jeppe Zacho, Michael A Nalls, Andrew B SingletonLuigi Ferrucci, John Hardy, Bradford B Worrall, Stephen S Rich, Mar Matarin, Paul E Norman, Leon Flicker, Osvaldo P Almeida, Frank M van Bockxmeer, Hiroshi Shimokata, Kay-Tee Khaw, Nicholas J Wareham, Martin Bobak, Jonathan A C Sterne, George Davey Smith, Philippa J Talmud, Cornelia van Duijn, Steve E Humphries, Jackie F Price, Shah Ebrahim, Debbie A Lawlor, Graeme J Hankey, James F Meschia, Manjinder S Sandhu, Aroon D Hingorani, Juan P Casas

    279 Citationer (Scopus)

    Abstract

    The MTHFR 677C→T polymorphism has been associated with raised homocysteine concentration and increased risk of stroke. A previous overview showed that the effects were greatest in regions with low dietary folate consumption, but differentiation between the effect of folate and small-study bias was difficult. A meta-analysis of randomised trials of homocysteine-lowering interventions showed no reduction in coronary heart disease events or stroke, but the trials were generally set in populations with high folate consumption. We aimed to reduce the effect of small-study bias and investigate whether folate status modifies the association between MTHFR 677C→T and stroke in a genetic analysis and meta-analysis of randomised controlled trials.
    OriginalsprogEngelsk
    TidsskriftLancet
    Vol/bind378
    Udgave nummer9791
    Sider (fra-til)584-94
    Antal sider11
    ISSN0140-6736
    DOI
    StatusUdgivet - 2011

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