Association between Tumor Necrosis Factor-α 308G/A Gene Polymorphism and Silicosis Susceptibility: A Meta-Analysis

Zhanzhan Li,Peng Chen,Shipeng Yan,Jing Xue,Lizhang Chen

doi:10.1371/journal.pone.0076614

Abstract

BackgroundTumor necrosis factor-α (TNF-α) 308 G/A gene polymorphism has been reported to be associated with susceptibility to silicosis. However, the relevant study results are still inconsistent.Objective and MethodsA meta-analysis was performed in order to drive a more precise estimation of the relationship between TNF-α-308 G/A gene polymorphism and susceptibility to silicosis. Electronic databases were searched and nine separate studies were included. The pooled odds ratios (ORs) and the corresponding 95% confidence internal (CI) were calculated by a fixed effect model.ResultsA total of 1267 cases and 1214 controls were included. In the overall analysis, significantly increased silicosis risk was found (for GA+AA vs. GG OR=1.45, 95%CI: 1.20-1.760, P=1.58E4; for GA vs. GG: OR=1.53, 95%CI=1.25-1.86, P=3.11E5; for A allele vs. G allele: OR=1.27, 95%CI=1.08-1.50, P= 0.004). In the subgroup analysis, significantly increased silicosis risk was also found among Asians (for GA+AA vs. GG: OR=1.63, 95%CI=1.27-2.08, P=1.01E4), for GA vs. GG: OR=1.71, 95%CI=1.33-2.20, P=3.44E5), for A allele vs. G allele: OR=1.45, 95%CI=1.17-1.80, P=0.001). However, no significantly increased risk was found among non-Asians for all genetic models.ConclusionsTNF-α-308 G/A polymorphism might lead to an increased risk of silicosis susceptibility, especially for Asians. However, further studies with large sample sizes should be conducted to confirm the association.

Highlights

Silicosis is one of the most important occupational diseases worldwide [1], which is considered a major public health problem in some developing countries such as India, South African and China
Knowledge Infrastructure for relevant studies published in English or Chinese(CNKI), WanFang, Database of Chinese Scientific and Technical Periodicals (VIP) were systematically searched using the following search terms: “tumor necrosis factor-α” or “tumor necrosis factor-alpha” or “TNF-α” or “TNFalpha” and “silicosis” combined with “polymorphism” or “mutation” or “variant ” and the last search was updated to April 25, 2013
The current meta-analysis suggests a significant relationship between TNF-α-308G/A gene polymorphism and silicosis risk under the dominant genetic model for 1.45(95%CI: 1.20-1.760), but no significant association is found under the recessive genetic model (OR=0.77, 95%CI: 0.46-1.29)

Summary

Introduction

Silicosis is one of the most important occupational diseases worldwide [1], which is considered a major public health problem in some developing countries such as India, South African and China. In a follow up study with an average duration of exposure to free silica of 16.8 years, an odds ratio (OR) of 2.75 was reported for the association of TB with silicosis [11]. Tumor necrosis factor-α (TNF-α) 308 G/A gene polymorphism has been reported to be associated with susceptibility to silicosis. Significantly increased silicosis risk was found (for GA+AA vs GG OR=1.45, 95%CI: 1.20-1.760, P=1.58E4; for GA vs GG: OR=1.53, 95%CI=1.25-1.86, P=3.11E5; for A allele vs G allele: OR=1.27, 95%CI=1.08-1.50, P= 0.004). Significantly increased silicosis risk was found among Asians (for GA+AA vs GG: OR=1.63, 95%CI=1.27-2.08, P=1.01E4), for GA vs GG: OR=1.71, 95%CI=1.33-2.20, P=3.44E5), for A allele vs G allele: OR=1.45, 95%CI=1.17-1.80, P=0.001). Conclusions: TNF-α-308 G/A polymorphism might lead to an increased risk of silicosis susceptibility, especially for Asians. Further studies with large sample sizes should be conducted to confirm the association

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Conclusion