Published online before print September 21, 2006, doi: 10.1161/01.STR.0000244782.76917.87
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(Stroke. 2006;37:2843.)
© 2006 American Heart Association, Inc.
Research Reports |
The Gene Encoding Transforming Growth Factor ß1 Confers Risk of Ischemic Stroke and Vascular Dementia
From the Ilsong Institute of Life Science, Hallym University, South Korea.
Correspondence to Chaeyoung Lee, PhD, Ilsong Institute of Life Science, Hallym University, 1605-4 Gwanyang-dong, Dongan-gu, Anyang, Kyonggi-do 431-060, South Korea. E-mail clee@hallym.ac.kr
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Abstract |
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Background and Purpose— Transforming growth factor-ß1 (TGF-ß1) is an anti-inflammatory cytokine that plays an important role in cerebrovascular pathophysiology with protective activity against ischemia-induced neuronal death. We investigated the association of the polymorphism in TGFB1 with ischemic stroke and vascular dementia.
Methods— Three sequence variants in and around promoter and exons of TGFB1 gene were identified in 30 Koreans. Pro10Leu was selected for association study, and then control subjects (n=207) and patients with ischemic stroke (n=271) and vascular dementia (n=207) were screened.
Results— Subjects carrying Leu/Leu were susceptible to both ischemic stroke (odds ratio [OR]=1.63; P<0.05) and vascular dementia (OR=1.88; P<0.01). Analyses with stroke subtypes showed a strong association with small vessel occlusion (SVO, n=110; OR=2.07; P<0.01). Further analysis of SVO data partitioned by gender revealed the female-specific association with Pro10Leu (OR=2.70; P<0.05).
Conclusions— The Pro10Leu of TGFB1 might be a risk factor of ischemic stroke and vascular dementia, especially for SVO in females.
Key Words: genetics • ischemia
An extract of the first 250 words of the full text is provided, because this article has no abstract. |
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Introduction |
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Transforming growth factor-ß1 (TGF-ß1) is an anti-inflammatory cytokine with neuroprotective activity against ischemia-induced neuronal death,1 and its expression increased in human brain tissue and cerebrospinal fluid after ischemia.2 We investigated the association of the TGFB1 gene with the risk of ischemic stroke and vascular dementia.
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Materials and Methods |
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Patients with ischemic stroke were recruited from Hallym University Hospital with the diagnosis by performing computed tomography or MRI scan from acute stroke patients within 7 days of onset (2002 to 2005). The stoke patients with dementia were excluded based on the criteria described in Kim et al.3 A total of 271 patients with ischemic stroke were further categorized into its subtypes using Trial of Org 10172 in Acute Stroke Treatment (TOAST) classification.4 As a result, 95 patients had large artery atherosclerosis, 110 had small vessel occlusion (SVO), and 20 had cardioembolism. Forty-six cases were diagnosed as stroke with other determined etiology or stroke of undetermined etiology. For details on the patients with vascular dementia and control subjects, see Kim et al.3 Written informed consent was obtained from all subjects. The study protocol was approved by the ethical committee.
Genomic DNA was isolated from peripheral blood cells using a commercially available kit from Qiagen. For detection of sequence variants in TGFB1, promoter, exons 1 to 7, and their flanking regions were screened in 30 random healthy subjects by direct sequencing. For the association study, Pro10Leu polymorphism was genotyped in patients and controls using TaqMan assay. The details on experiments are described in supplemental Appendix
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