Association of MTHFR C677T Genotype With Ischemic Stroke Is Confined to Cerebral Small Vessel Disease Subtype

Stroke; a Journal of Cerebral Circulation
Loes C A Rutten-JacobsHugh S Markus

Abstract

Elevated plasma homocysteine levels are associated with stroke. However, this might be a reflection of bias or confounding because trials have failed to demonstrate an effect from homocysteine lowering in stroke patients, although a possible benefit has been suggested in lacunar stroke. Genetic studies could potentially overcome these issues because genetic variants are inherited randomly and are fixed at conception. Therefore, we tested the homocysteine levels-associated genetic variant MTHFR C677T for association with magnetic resonance imaging-confirmed lacunar stroke and compared this with associations with large artery and cardioembolic stroke subtypes. We included 1359 magnetic resonance imaging-confirmed lacunar stroke cases, 1824 large artery stroke cases, 1970 cardioembolic stroke cases, and 14 448 controls, all of European ancestry. Furthermore, we studied 3670 ischemic stroke patients in whom white matter hyperintensities volume was measured. We tested MTHFR C677T for association with stroke subtypes and white matter hyperintensities volume. Because of the established association of homocysteine with hypertension, we additionally stratified for hypertension status. MTHFR C677T was associated with lacunar stroke (P=0....Continue Reading

References

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Citations

Sep 1, 2018·JAMA Neurology·Robert W RegenhardtLouis R Caplan
Jan 9, 2019·Annals of the New York Academy of Sciences·Loes C A Rutten-Jacobs, Natalia S Rost
Jan 22, 2019·Stroke; a Journal of Cerebral Circulation·Hugh S Markus, Reinhold Schmidt
Feb 21, 2019·Annals of Neurology·Susanna C LarssonHugh S Markus
Mar 19, 2019·International Journal of Immunogenetics·Arezou SayadSoudeh Ghafouri-Fard
Feb 18, 2017·Nature Reviews. Neurology·Vincent C T MokLawrence K S Wong
Feb 24, 2019·Neurology·Martin SöderholmUNKNOWN International Stroke Genetics Consortium, the NINDS-SiGN Consortium, and the Genetics of Ischaemic Stroke Functional Outcome
May 23, 2020·Current Atherosclerosis Reports·Minghua Liu, Jose Gutierrez
Sep 6, 2018·Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism·Christoph J GriessenauerClemens M Schirmer
Feb 27, 2020·The International Journal of Neuroscience·Mehrdokht MazdehSoudeh Ghafouri-Fard
Jul 1, 2019·Clinical Neurology and Neurosurgery·Marina Yurievna MaksimovaAslan Amirkhanovich Kubatiev
Aug 3, 2019·Journal of the Neurological Sciences·Yifan JiYanhong Dong
Dec 2, 2020·Journal of Stroke and Cerebrovascular Diseases : the Official Journal of National Stroke Association·Yifan JiPei Yuan Lv
Dec 31, 2020·European Journal of Neurology : the Official Journal of the European Federation of Neurological Societies·Yuze CaoJun Ni
Mar 7, 2021·International Journal of Molecular Sciences·Rita MorettiClaudio Tiribelli

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Methods Mentioned

BETA
genotyping

Software Mentioned

EIGENSTRAT
PLINK
IMPUTE

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