title: GTP cyclohydrolase 1 gene 3'-UTR C+243T variant predicts worsening outcome in patients with first-onset ischemic stroke.
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.
authors.affiliation: 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
authors.forename: Ling
authors.initials: L
authors.lastname: Tang
authors.forename: Lan
authors.initials: L
authors.lastname: Zhang
authors.forename: Hu
authors.initials: H
authors.lastname: Ding
authors.forename: Wei
authors.initials: W
authors.lastname: Tu
authors.forename: Jiangtao
authors.initials: J
authors.lastname: Yan
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics*; D000368:Aged; D002545:Brain Ischemia / Q000235:genetics; D005260:Female; D006136:GTP Cyclohydrolase / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009569:Nitric Oxide / Q000378:metabolism; D011379:Prognosis; D012307:Risk Factors; D020521:Stroke / Q000175:diagnosis / Q000235:genetics*
chemical_list: D020413:3' Untranslated Regions; D009569:Nitric Oxide; D006136:GTP Cyclohydrolase