Role for mitochondrial uncoupling protein-2 (UCP2) in hyperhomocysteinemia and venous thrombosis risk?
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.
Laboratory of Pediatrics and Neurology, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands. sandra.heil@wur.nl
Sandra G
SG
Heil
Sita H
SH
Vermeulen
Brenda J M
BJ
Van der Rijt-Pisa
Martin
M
den Heijer
Henk J
HJ
Blom
D000328:Adult; D000368:Aged; D005260:Female; D006801:Humans; D020138:Hyperhomocysteinemia / Q000235:genetics*; D007473:Ion Channels / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D024101:Mitochondrial Proteins / Q000235:genetics*; D011110:Polymorphism, Genetic; D012307:Risk Factors; D014475:Uncoupling Agents; D000071246:Uncoupling Protein 2; D020246:Venous Thrombosis / Q000235:genetics*
D007473:Ion Channels; D024101:Mitochondrial Proteins; C000604389:UCP2 protein, human; D014475:Uncoupling Agents; D000071246:Uncoupling Protein 2