| BackgroundIschemice stroke(IS) is manifested by the abrupt onset of focal neurologic deficits, which were caused by a suddent reduction or completely blockage of blood supply to local brain tissues. IS is a leading cause of death and adult long-term disability worldwide, and remains as an enormous burden for personality and society due to lack of illustrated etiology and effective treatments.IS is a multifactorial disease involving complex interactions between genetic and environmental factors, in which the genetic susceptibility has been considered playing an important role in the development of IS. With the accomplishment of the human genome project and the development of molecular genetics, the study on the single neucleotide polymorphism(SNP), which can reflect the variance among individuals and decide the susceptibility of diseases and response to drugs, is highly regarded as one of the most important post-genomic projects. Identification of the candidate gene susceptibility to IS has also become one of the most popular scientific focuses. Recently, emerging evidences have demonstrated that inflammation play an important role in the pathogenesis of IS. As one of the candidate susceptible gene of IS, the functional polymorphisms of inflammatory factors arouse close attentions.TGF-β1is a pleiotropic cytokine with potent anti-inflammation property, and has been considered as an essential risk factor in the inflammatory process of IS. The TGF-β1gene is located on chromosome19(q13.1-13.3) with several common known SNPs in this gene. Among them, T869C (rs1982073; Leu10/Pro10; T29C; codon10) polymorphism, located in the signal peptide sequence, has been indicated that it can increase the expression of TGF-β1mRNA, resulting in the elevated serum TGF-β1level.To date, several studies have been performed to investigate the association between T869C polymorphism of TGF-β1gene and risk of IS. However, the results remain controversial. Considering a single study may lack the power to provide reliable conclusion due to small amount of subjects, masses of statistical and clinical heterogeneities, we performed this meta-analysis combining eligible published literatures based on quantitative synthesis to derive a more convincing estimation for the association between T869C polymorphism and risk of IS.ObjectiveTo explore the association between TGF-β1T869C polymorphism and risk of ischemic stroke by performing a meta-analysis based on published articles.MethodsSystematic electronic searches of PubMed, Cochrane Library, Science Direct, BIOSIS Previews, Chinese Biomedical Database, Chinese National Knowledge Infrastructure, and WANGFANG Database until March2013were performed to idetify the published epidemiological studies on TGF-β1T869C polymorphism and risk of ischemic stroke. Strict inclusion and exclusion criteria were determined before data analyses. Data were reviewed and extracted by2independent investigators. Quality of the included studies was evaluated independently using Newcastle-Ottawa Scale (NOS). The strength of association between TGF-β1T869C polymorphism and IS risk was assessed by crude ORs with corresponding95%CIs under the following five genetic models:the allele comparison(C vs. T), the homozygote comparison (CC vs. TT), the heterozygote comparison (CT vs. TT), the dominant model (CC+CT vs. TT), and the recessive model (CC vs. CT+TT). The degree of heterogeneity between studies was detected by the Q-test and I2-statistics. The pooled estimate was combined by a random-effect model(DerSimonian-Laird method) or a fixed-effect model (Mantel-Haenszel method) according to whether the heterogeneity existed or not. Subgroup analysis based on ethnicity, source of controls, and study design were further conducted respectively to explore the potential sources of heterogeneity. Sensitivity analysis was performed to elucidate the stability of the outcomes. Publication bias was evaluated by funnel plot and Egger’s test. All analyses were conducted using RevMan5.1and Stata12.0software.ResultsA total of6studies involving1701cases and10334controls were included in this meta-analysis. The overall estimates did not show any significant association between TGF-β1T869C polymorphism and risk of IS under all genetic models (allele comparison C vs. T:OR=1.08,95%CI=0.88-1.32; homozygote comparison CC vs. TT: OR=1.17,95%CI=0.79-1.72; heterozygote comparison CT vs. TT:OR=0.91,95%CI=0.68-1.22; dominant model CC+CT vs. TT:OR=0.99,95%CI=0.73-1.35; recessive model 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, a 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 a significant decreased risk was detected under heterozygote comparison(CT vs. CC:OR=0.72,95%CI=0.57-0.92) in the case-control studies. Sensitivity analysis did not significantly alter in overall and subgroup results under all genetic models; In addition, results from funnel plot and Egger’s test indicated no evidence of publication bias.Conclusion1. Upon the results of this meta-analysis, it implied that the current epidemiological studies of TGF-β1T869C polymorphism were too inconsistent to draw a conclusion on the association with IS susceptibility.2. Given the small sample size and the remarkable heterogeneity in it, more well-designed prospective large-scale studies with different ethnicities considering both genetic and environmental factors will be performed further in future. |
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