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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.

Artikel i vetenskaplig tidskrift
Författare Hultdin Johan
Bethany Van Guelpen
Anna Winkvist
Göran Hallmans
Lars Weinehall
Birgitta Stegmayr
Torbjörn Nilsson
Publicerad i Clinical Chemistry and Laboratory Medicine
Volym 49
Nummer/häfte 9
Sidor 1555-1562
ISSN 1434-6621
Publiceringsår 2011
Publicerad vid Institutionen för medicin, avdelningen för klinisk näringslära
Sidor 1555-1562
Språk en
Länkar dx.doi.org/10.1515/CCLM.2011.234
Ämnesord cerebral hemorrhage; homocysteine; MTHFR;risk factors; stroke.
Ämneskategorier Klinisk kemi, Folkhälsomedicinska forskningsområden

Sammanfattning

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 wOR for the highest vs. lowest tHcy quartile 8.13 (95% CI 1.83–36.1), ptrends0.002; OR for MTHFR 677TT vs. 677CC genotype 3.62 (95% CI 0.77–17.0), ptrends0.040x. Haplotype analyses confirmedthat the MTHFR 677T–1298A haplotype was positively associated with hemorrhagic stroke wOR 1.81 (95% CI 1.09–3.00), ps0.022x, 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.

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