GTP cyclohydrolase 1 gene 3′-UTR C+243T variant predicts worsening outcome in patients with first-onset ischemic stroke |
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Authors: | Ling Tang Lan Zhang Hu Ding Wei Tu Jiangtao Yan |
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Institution: | (1) Department of Molecular Neuroscience, Institute of Neurology, Queen Square, London, WC1N 3BG, UK;(2) Neurometabolic Unit, National Hospital, Queen Square, 105, London, WC1N 3BG, UK; |
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Abstract: | Tetrahydrobiopterin (BH4) is an essential cofactor for all three nitric oxide synthase (NOS isoforms), which plays an important
role in vascular diseases. GTP cyclohydrolase 1 (GCH 1) is the first-step and rate-limiting enzyme for BH4 biosynthesis in
its de novo pathway. Common GCH1 gene variant C+243T in the 3′-untranslated region predicts NO excretion. The present study examined
the predictive role of GCH 1 gene 3′-UTR C+243T variant in the long-term outcome of ischemic stroke. A total of 142 patients
with first-onset ischemic stroke were recruited and detected for genotype of GCH1 3′-UTR C+243T by a TaqMan SNP Genotyping
assay. Subsequent vascular events and death were determined over a 5-year follow-up period. The frequency of GCH1 3′-UTR +243
C/T or T/T genotype was significantly increased in patients with endpoint events as compared with those without events (74%
vs 57.8%, P=0.06). Cox regression survival analysis indicated that an increased probability of death or new vascular events was found
in patients with GCH1 3′-UTR +243 C/T or T/T genotype compared with those with GCH1 3′-UTR C/C genotype (40.6% vs 25.5%), GCH1 3′-UTR +243 C/T or T/T genotype relative to GCH1 3′-UTR C/C genotype was associated with the increased risk
of death or vascular events even after adjustment for other risk factors (OR=2.171, 95% CI: 1.066–4.424, P=0.033). It was concluded that GCH1 3′-UTR C+243T variant was an independent predictor of worsening long-term outcomes in
patients with first-onset ischemic stroke. |
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Keywords: | GTP cyclohydrolase 1 ischemic stoke outcome gene polymorphism |
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