GTP cyclohydrolase 1 gene 3'-UTR C+243T variant predicts worsening outcome in patients with first-onset ischemic stroke.
10.1007/s11596-010-0642-y
- Author:
Ling TANG
1
;
Lan ZHANG
;
Hu DING
;
Wei TU
;
Jiangtao YAN
Author Information
1. Institute of Hypertension and Department of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China. tonny.tl@yeah.net
- Publication Type:Journal Article
- MeSH:
3' Untranslated Regions;
genetics;
Aged;
Brain Ischemia;
genetics;
Female;
GTP Cyclohydrolase;
genetics;
Humans;
Male;
Middle Aged;
Nitric Oxide;
metabolism;
Prognosis;
Risk Factors;
Stroke;
diagnosis;
genetics
- From:
Journal of Huazhong University of Science and Technology (Medical Sciences)
2010;30(6):694-698
- CountryChina
- Language:English
-
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.
