Abstract
ObjectiveTo explore the association between transforming growth factor-beta1 (TGF-β1) T869C polymorphism and risk of ischemic stroke (IS) by performing a meta-analysis based on published articles.MethodsSystematic electronic searches of PubMed, Science Direct, BIOSIS Previews, Chinese Biomedical Database, Chinese National Knowledge Infrastructure, and WANFANG Database were performed. The strength of the association was calculated by pooled odds ratios (ORs) with 95% confidence intervals (95%CIs). Subgroup analysis was conducted to explore potential sources of heterogeneity. Sensitivity analysis was performed to elucidate the stability of the outcomes. Publication bias was evaluated by Begg’s funnel plot and Egger’s test.ResultsA total of 6 studies involving 1701 cases were included. The overall estimates did not show any significant association between TGF-β1 T869C polymorphism and risk of IS under all genetic models (C vs. T: OR = 1.08,95%CI = 0.88–1.32; CC vs. TT:OR = 1.17,95%CI = 0.79–1.72; CT vs. TT: OR = 0.91, 95%CI = 0.68–1.22; CC+CT vs. TT: OR = 0.99, 95%CI = 0.73–1.35; CC vs. CT+TT: OR = 1.23, 95%CI = 0.95–1.59). Similar lacking associations were observed in subgroup analysis based on ethnicity and source of controls. When stratified by study design, significant increased association of IS risk was found in cohort studies under genetic models except recessive model(C vs. T: OR = 1.18, 95%CI = 1.05–1.32; CC vs. TT: OR = 1.40, 95%CI = 1.10–1.77; CT vs. TT: OR = 1.23, 95%CI = 1.02–1.49; CC+CT vs. TT: OR = 1.27, 95%CI = 1.03–1.57; CC vs. CT+TT, OR = 1.21, 95%CI = 0.99–1.47), whereas in case-control studies a significant decreased risk was detected under heterozygote comparison(CT vs. CC: OR = 0.72, 95%CI = 0.57–0.92). However, after correction for multiple testing, the associations were observed to be null significant in both cohort and case-control subgroups among all genetic models.ConclusionThis meta-analysis suggested that current epidemiological studies of TGF-β1 T869C polymorphism are too inconsistent to draw a conclusion on the association with IS susceptibility. Given the small sample size and remarkable between-study heterogeneity, further well-designed prospective large-scale studies are warranted.
Highlights
Stroke is a leading cause of death and adult long-term disability worldwide, and remains as an enormous burden for society due to lack of illustrated etiology and effective treatments [1]
The genetic polymorphisms of transforming growth factor-beta1 (TGF-b1) can affect the level of its production.The TGF-b1 gene is located on chromosome 19(q13.1–13.3), including 7 exons and 6 introns
With a transition from T to C resulting in a substitution of leucine to proline, the T869C single nucleotide polymorphisms (SNPs) was reported to be associated with elevated serum concentration of TGF-b1 [6]
Summary
Stroke is a leading cause of death and adult long-term disability worldwide, and remains as an enormous burden for society due to lack of illustrated etiology and effective treatments [1]. TGF-b1 is a pleiotropic cytokine with potent anti-inflammation property, and has been considered as an essential risk factor in the inflammatory process of IS by involving in the pathophysiological progresses of such as hypertension, atherosclerosis and lipid metabolisms [4]. The genetic polymorphisms of TGF-b1 can affect the level of its production.The TGF-b1 gene is located on chromosome 19(q13.1–13.3), including 7 exons and 6 introns. T869C (rs1982073; Leu10/Pro; T29C, codon10) in exon 1 of the TGF-b1 gene is located at position 10 in the signal peptide; this sequence allows export of the newly synthesized protein across membranes of the endoplasmic reticulum. Further functional experiments have been indicated that T869C polymorphism can increase the expression of TGF-b1 mRNA by influencing the intracellular trafficking or exporting efficiency of the synthesized protein to the endoplasmic reticulum, resulting in the elevated serum TGF-b1 level [7]
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