Association between transforming growth factor-beta 1 T869C polymorphism and ischemic stroke: a meta-analysis

Abstract

Objective: To 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.

Methods: Systematic 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.

Results: A 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.

Conclusion: This 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.

Figure 1. Flow diagram of the selection of eligible studies.

Figure 2. Forest plot for association between TGF-β1 T869C polymorphism and IS risk based on study design.

(A) Allele comparison(C vs. T); (B) Homozygote comparison (CC vs. TT); (C) Heterozygote comparison (CT vs. TT); (D) Dominant model (CC+CT vs. TT); (E) Recessive model (CC vs. CT+TT).