The Gene Encoding Transforming Growth Factor β1 Confers Risk of Ischemic Stroke and Vascular Dementia

Abstract

BACKGROUND AND PURPOSE: Transforming growth factor-beta1 (TGF-beta1) 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.