Role for mitochondrial uncoupling protein-2 (UCP2) in hyperhomocysteinemia and venous thrombosis risk?

S.G. Heil, S.H. Vermeulen, B.J. Rijt-Pisa, M. den Heijer, H.J. Blom

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    Abstract

    Background: Hyperhomocysteinemia has been associated with an increased risk of venous thrombosis, which might be mediated through an oxidative stress dependent mechanism. The function of uncoupling protein-2 (UCP2) is still under debate, but it has been suggested to play a role in reduction of mitochondrial reactive oxygen species. In the present study, we investigated whether the 45 bp deletion/insertion (del/ins) polymorphism in the UCP2 gene is associated with elevated homocysteine levels and whether it might be associated with an increased risk of recurrent venous thrombosis (RVT). Methods: The 45 bp del/ins polymorphism in the UCP2 gene was genotyped by PCR analysis in 161 RVT cases and 386 controls of Caucasian origin in which fasting- and post-load homocysteine levels were previously determined. Statistical analysis was performed to assess whether the UCP2 45 bp del/ins polymorphism was associated with plasma total homocysteine levels and venous thrombosis risk. Results: Post-load homocysteine levels were positively associated with UCP2 45 bp ins/ins genotype (p=0.02). None of the UCP2 45 bp ins/del genotypes were associated with fasting plasma homocysteine levels. The frequency of the UCP2 45 bp ins/ins genotype was 12.4% in RVT cases compared to 8.3% in controls, which resulted in an odds ratio of 1.8 (95% CI 1.0¿3.4). Conclusions: The results of our study show that the common 45 bp del/ins polymorphism in the UCP2 gene is associated with hyperhomocysteinemia, which might increase the risk of venous thrombosis. However, the mechanism is not fully understood and additional studies should be performed to confirm our findings.
    Original languageEnglish
    Pages (from-to)655-659
    JournalClinical Chemistry and Laboratory Medicine
    Volume46
    Issue number5
    DOIs
    Publication statusPublished - 2008

    Keywords

    • homocysteine
    • translocation
    • metaanalysis
    • activation
    • obesity
    • disease
    • trial
    • cells
    • mthfr

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