Association between tumor necrosis factor-alpha 857C/T polymorphism and susceptibility to ankylosing spondylitis: a meta-analysis

English Keywords:Ankylosing spondylitis  Tumor necrosis factor-alpha  Single nucleotide polymorphism  Meta-analysis

English Abstract:

  【Abstract】 Objectives: To explore the association between the polymorphism in -857 site of tumor necrosis factor(TNF)-α promoter region and the susceptibility to ankylosing spondylitis(AS). Methods: Case-control studies Pubmed, Cochrane Library, Ovid, Chinese Biomedical Database(CBM), Chinese National Knowledge Infrastructure(CNKI), Wanfang and Weipu data bases from inception to October 2013 for the association between TNF-α-857 C/T polymorphism and the susceptibility to AS were collected. Meta-analysis was performed by Revman 5.2 and Stata 12.0 software. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were derived from random-effects or fixed-effects models to assess the strength of the association. Results: Nine case-control studies were included in the final meta-analysis, including a total of 933 AS patients and 1094 controls. Statistically significant differences between AS and control groups were observed in the susceptibility to AS and TNF-α-857 genotype CC [OR=0.46, 95%CI (0.26, 0.81), P=0.007], allele C [OR=0.61, 95%CI (0.41, 0.91), P=0.02] and T [OR=1.64, 95%CI (1.10, 2.43), P=0.02]. But, no statistical difference in the frequency of genotype TT [OR=1.49, 95%CI (0.95, 2.34), P=0.08] was observed between AS and control groups. There were obvious heterogeneities among the studies of genotype CC(P<0.00001, I2=87%), allele C(P<0.00001, I2=84%) and allele T(P<0.00001, I2 =84%), except genotype TT(P=0.09, I2=42%). Sensitivity analysis was performed by leaving out one study at a time, but the heterogeneity remained obvious. It was symmetric of the funnel plots of genotype CC, allele C and T with AS, but genotype TT. There was no statistical significance in genotype CC[Begg′s test(z=0.52, P=0.602), Egger′s test(t=0.23, P=0.825)], genotype TT[Begg′s test(z=0.94, P=0.348), Egger′s test(t=1.26, P=0.248)], allele C[Begg′s test(z=0.31, P=0.754), Egger′s test(t=0.72, P=0.494)] or allele T[Begg′s test(z=0.31, P=0.754), Egger′s test(t=－0.72, P=0.494)]. Conclusions: Genotype CC, allele C and T of TNF-α-857 are associated with the susceptibility to AS, and T-allele carriers have higher risk of AS.