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Background: Transforming growth factor-beta 1 (TGF-β1) is a multifunctional pleiotropic cytokine involved in inflammation and pathogenesis of cerebrovascular diseases. There is limited information on the association between variations within the TGF-β1 gene polymorphisms and risk of ischemic stroke (IS). The aim of this study was to investigate the association of the TGF-β1 gene (C509T, G800A, and T869C) polymorphisms, and their haplotypes with the risk of IS in North Indian population. Methods: A total of 250 IS patients and 250 age- and sex-matched controls were studied. IS was classified using the Trial of Org 10172 in Acute Stroke Treatment classification. Conditional logistic regression analysis was used to calculate the strength of association between TGF-β1 gene polymorphisms and risk of IS. Genotyping was performed using SNaPshot method. Results: Hypertension, diabetes, dyslipidemia, alcohol, smoking, family history of stroke, sedentary lifestyle, and low socioeconomic status were found to be associated with the risk of IS. The distribution of C509T, G800A and T869C genotypes was consistent with Hardy-Weinberg Equilibrium in the IS and control groups. Adjusted conditional logistic regression analysis showed a significant association of TGF-β1 C509T (odds ratio [OR], 2.1; 95% CI; 1.2–3.8; P = 0.006), G800A (OR, 4.4; 95% CI; 2.1–9.3; P < 0.001) and T869C (OR, 2.6; 95% CI; 1.5–4.5; P = 0.001) with the risk of IS under dominant model. Haplotype analysis showed that C509-A800-T869 and T509-G800-C869 haplotypes were significantly associated with the increased risk of IS. C509T and T869C were in strong linkage disequilibrium (D’ =0.51, r2 = 0.23). Conclusion: Our results suggest that TGF-β1 polymorphisms and their haplotypes are significantly associated with the risk of IS in North Indian population. [ABSTRACT FROM AUTHOR]

Introduction: Transforming Growth Factor-Beta 1 (TGF-β1) is a pleiotropic cytokine with potent anti-inflammatory property, which has been considered as an essential risk factor in the inflammatory process of Ischemic Stroke (IS), by involving in the pathophysiological progression of hypertension, atherosclerosis, and lipid metabolisms. -509C/T TGF-β1 gene polymorphism has been found to be associated with the risk of IS. The aim of this meta-analysis was to provide a relatively comprehensive account of the relation between -509C/T gene polymorphisms of TGF-β1 and susceptibility to IS. Methods: A review of literature for eligible genetic association Studies published before October 20, 2014 was conducted in the PubMed, EMBASE, Google Scholar and Trip database. The strength of association was calculated by pooled odds ratios (ORs) with 95% confidence intervals using RevMan 5.3 software. Heterogeneity was examined using Higgins I-squared, Tau-squared, and Chi-squared tests. Results: A total of 2 studies involving 614 cases and 617 controls were found. The overall estimates did not show any significant relation between TGF-β1-509C/T polymorphism and risk of IS under dominant (CC+CT vs. TT: OR=1.01, 95%CI=0.31 to 3.26; P=0.99), recessive (CC vs. CT+TT: OR=0.94, 95%CI=0.47 to 1.90; P=0.87), and allelic models (T vs. C: OR=1.06, 95%CI=0.55 to 2.04; P=0.86). Conclusion: This meta-analysis showed that TGF-β1-509C/T gene polymorphism has no significant association with the susceptibility of IS. Further well-designed prospective studies with larger sample size are needed to confirm these findings. [ABSTRACT FROM AUTHOR]