Role of promoter polymorphisms in the plasma glutathione peroxidase (GPx-3) gene as a risk factor for cerebral venous thrombosis
- PMID: 18096833
- DOI: 10.1161/STROKEAHA.107.490094
Role of promoter polymorphisms in the plasma glutathione peroxidase (GPx-3) gene as a risk factor for cerebral venous thrombosis
Abstract
Background and purpose: Plasma glutathione peroxidase (GPx-3) is a major antioxidant enzyme in plasma and the extracellular space that scavenges reactive oxygen species produced during normal metabolism or after oxidative insult. A deficiency of this enzyme increases extracellular oxidant stress, promotes platelet activation, and may promote oxidative posttranslational modification of fibrinogen. We recently identified a haplotype (H(2)) in the GPx-3 gene promoter that increases the risk of arterial ischemic stroke among children and young adults.
Methods: The aim of this study is to identify possible relationships between promoter haplotypes in the GPx-3 gene and cerebral venous thrombosis (CVT). We studied the GPx-3 gene promoter from 23 patients with CVT and 123 young controls (18 to 45 years) by single-stranded conformational polymorphism and sequencing analysis.
Results: Over half of CVT patients (52.1%) were heterozygous (H(1)H(2)) or homozygous (H(2)H(2)) carriers of the H(2) haplotype compared with 12.2% of controls, yielding a more than 10-fold independent increase in the risk of CVT (OR=10.7; 95% CI, 2.70 to 42.36; P<0.0001). Among women, the interaction of the H(2) haplotype with hormonal risk factors increased the OR of CVT to almost 70 (P<0.0001).
Conclusions: These findings show that a novel GPx-3 promoter haplotype is a strong, independent risk factor for CVT. As we have previously shown that this haplotype is associated with a reduction in transcriptional activity, which compromises antioxidant activity and antithrombotic benefits of the enzyme, these results suggest that a deficiency of GPx-3 leads to a cerebral venous thrombophilic state.
Comment in
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No association of the plasma glutathione peroxidase (GPx-3) gene with cerebral venous thrombosis in the German population.Stroke. 2009 Feb;40(2):e24; author reply e25. doi: 10.1161/STROKEAHA.108.540062. Epub 2008 Dec 18. Stroke. 2009. PMID: 19095977 No abstract available.
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