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Licensed Unlicensed Requires Authentication Published by De Gruyter June 15, 2011

Prospective study of first stroke in relation to plasma homocysteine and MTHFR 677C>T and 1298A>C genotypes and haplotypes – evidence for an association with hemorrhagic stroke

  • Johan Hultdin , Bethany Van Guelpen , Anna Winkvist , Göran Hallmans , Lars Weinehall , Birgitta Stegmayr and Torbjörn K. Nilsson EMAIL logo

Abstract

Background: Abnormalities in homocysteine metabolism have been suggested as risk factors for stroke. The aim of this prospective study was to examine whether total plasma homocysteine concentration (tHcy) and its main genetic determinant, methylene tetrahydrofolate reductase (MTHFR) polymorphisms, were associated with first ischemic or hemorrhagic stroke.

Methods: This was a nested case-referent study of 321 ischemic and 60 hemorrhagic stroke cases, defined by WHO MONICA criteria and each matched with two event-free referents for sex, age, cohort, recruitment date and geographical area. All subjects were from the population-based Northern Sweden Health and Disease Study cohorts. Odds ratios were determined by conditional logistic regression.

Results: The mean follow-up time was 4.2 years. Both tHcy and MTHFR were independent predictors of hemorrhagic stroke in multivariate models including body mass index, hypertension and, for MTHFR, tHcy [OR for the highest vs. lowest tHcy quartile 8.13 (95% CI 1.83–36.1), ptrend=0.002; OR for MTHFR 677TT vs. 677CC genotype 3.62 (95% CI 0.77–17.0), ptrend=0.040]. Haplotype analyses confirmed that the MTHFR 677T–1298A haplotype was positively associated with hemorrhagic stroke [OR 1.81 (95% CI 1.09–3.00), p=0.022], whereas the MTHFR 677C–1298C haplotype was not significantly related to either hemorrhagic or ischemic stroke. Neither tHcy nor the MTHFR polymorphisms were significant predictors of ischemic stroke.

Conclusion: Both elevated plasma homocysteine levels and the MTHFR 677T allele are indicators of increased risk of hemorrhagic stroke in the northern Swedish population.


Corresponding author: Torbjörn K. Nilsson, Department of Laboratory Medicine, Örebro University Hospital, Örebro, Sweden Phone: +46-19-602-1733, Fax: +46-19-602-3785

Received: 2010-12-20
Accepted: 2011-4-19
Published Online: 2011-06-15
Published in Print: 2011-09-01

©2011 by Walter de Gruyter Berlin Boston

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