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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
Published/Copyright: June 15, 2011
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Clinical Chemistry and Laboratory Medicine
From the journal Clinical Chemistry and Laboratory Medicine Volume 49 Issue 9

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.

Keywords: cerebral hemorrhage; homocysteine; MTHFR; risk factors; stroke
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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https://doi.org/10.1515/CCLM.2011.234
Keywords for this article
cerebral hemorrhage; homocysteine; MTHFR; risk factors; stroke

Articles in the same Issue

  1. Editorial
  2. Athlete's biological passport: to test or not to test?
  3. Review
  4. Prognostic value of cystatin C in acute coronary syndromes: enhancer of atherosclerosis and promising therapeutic target
  5. Opinion Papers
  6. The function of oxalic acid in the human metabolism
  7. Current limitations of the Athlete's Biological Passport use in sports
  8. Limits and pitfalls of Athlete's Biological Passport
  9. The Athlete Biological Passport from the perspective of an anti-doping organization
  10. Perspectives
  11. Genetics of infectious diseases: hidden etiologies and common pathways
  12. Guidelines and Recommendations
  13. IFCC primary reference procedures for the measurement of catalytic activity concentrations of enzymes at 37 °C. Part 9: Reference procedure for the measurement of catalytic concentration of alkaline phosphatase
  14. Genetics and Molecular Diagnostics
  15. A template for mutational data analysis of the CFTR gene
  16. High resolution melting analysis to genotype the most common variants in the HFE gene
  17. General Clinical Chemistry and Laboratory Medicine
  18. Bayesian analysis of an international ELISA comparability study
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  26. Determinants of oxidative stress related to gender: relevance of age and smoking habit
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