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Meta-Analysis
. 2019 Mar 25;52(3):e7927.
doi: 10.1590/1414-431X20187927.

Association between tumor necrosis factor polymorphisms and rheumatoid arthritis as well as systemic lupus erythematosus: a meta-analysis

Lin Chen  1 , Zhuochun Huang  2 , Yun Liao  2 , Bin Yang  2 , Junlong Zhang  2
Affiliations
Meta-Analysis

Association between tumor necrosis factor polymorphisms and rheumatoid arthritis as well as systemic lupus erythematosus: a meta-analysis

Lin Chen et al. Braz J Med Biol Res. .

Abstract

Tumor necrosis factor-alpha (TNF-α) plays an important role in autoimmune diseases. Previous studies have investigated the association of TNF-α-238G/A (rs361525) and -308G/A (rs1800629) polymorphisms with rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). However, no agreed conclusion had been made. Therefore, this meta-analysis was conducted to assess the associations of TNF-α-238G/A and -308G/A polymorphisms with RA and SLE risk. A systematic search was conducted in commonly used databases. Meta-analysis was performed by STATA12.0. A total of 43 studies were included. In the overall population, the TNF-α-238A allele was observed to be a protective factor for RA (A vs G: OR=0.75, 95%CI=0.57-0.99, P=0.040) and the TNF-α-308A allele was found to be a risk factor for SLE (A vs G: OR=1.78, 95%CI=1.45-2.19, P<0.001). However, no evidence of association was found between TNF-α-238 G/A polymorphism and SLE nor between -308G/A and RA. In the subgroup analysis, TNF-α-308A allele played a pathogenic role for RA in Latin Americans (A vs G: OR=1.46, 95%CI=1.15-1.84, P=0.002) and for SLE in Latin Americans (A vs G: OR=2.12, 95%CI=1.32-3.41, P=0.002) and Europeans (A vs G: OR=2.03, 95%CI=1.56-2.63, P<0.001), while it played a protective role for RA in Asians (A vs G: OR=0.54, 95%CI=0.32-0.90, P=0.017). No significant association was found between TNF-α-308G/A and SLE susceptibility in Africans and Asians. This meta-analysis demonstrated that TNF-α-238A was associated with decreased risk of RA rather than SLE, while -308G/A polymorphism was associated with SLE rather than RA. Stratification analysis indicated that different ethnicities would have different risk alleles.

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Figures

Figure 1
Figure 1. Flow chart illustrating the selection of articles included in the meta-analysis. SNP: single-nucleotide polymorphisms; RA: rheumatoid arthritis; SLE: systemic lupus erythematosus; HWE: Hardy-Weinberg equilibrium.
Figure 2
Figure 2. Forest plot for the correlation between TNF-α-238 and rheumatoid arthritis (A) and systemic lupus erythematosus (B) risk.
Figure 3
Figure 3. Forest plot for the correlation between TNF-α-308 and rheumatoid arthritis (A) and systemic lupus erythematosus (B) risk.
Figure 4
Figure 4. Funnel plots of publication bias for meta-analysis of TNF-α-308 and rheumatoid arthritis (A) and systemic lupus erythematosus (B).
See this image and copyright information in PMC

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