Tumor Necrosis Factor-α G-308A Polymorphism and Sporadic IgA Nephropathy: A Meta-Analysis Using a Genetic Model-Free Approach

Abstract

Tumor necrosis factor-α (TNF-α) is a potent pro-inflammatory cytokine, involved in the pathogenesis and progression of immunoglobulin A nephropathy (IgAN). A bi-allelic polymorphism in the promoter region, at position -308 (G/A) of the TNF-α gene (rs1800629) is associated with an increased TNF-a production. However, several previous association studies of TNF-α G-308A polymorphism and IgAN rendered contradictory findings. The objective of the present study is to shed light on these inconclusive results and clarify the role of TNF-α and any possible contribution of this factor in the development and progression of sporadic IgAN. Therefore, a meta-analysis of all available genetic association studies relating the TNF-α G-308A polymorphism to the risk for development and/or progression of IgAN was conducted. Seven studies were included in the meta-analysis. Three of them included populations of European descent (Caucasians) and four involved Asians. The generalized odds ratio (OR_G) was used to estimate the risk for the development and/or progression of the disease. Overall, the meta-analysis did not detect any significant association between the G-308A variant and both the risk of developing IgAN and the risk for progression of IgAN. In conclusion, these results suggest that TNF-α does not constitute a key component in the genetic architecture of sporadic IgAN. However, further evidence deciphering the influence of TNF-α on IgAN is still needed.

Keywords: TNF-α; immunoglobulin A nephropathy (IgAN); meta-analysis; polymorphism; tumor necrosis factor-α.

Figure 1

PRISMA 2020 flow diagram of retrieved articles with specifications of reasons for exclusion.

Figure 2

Forest plot of TNF-α G-308A polymorphism and the risk of sporadic IgA nephropathy in main analysis [23,24,25,26,27,28,29].

Figure 3

Forest plot of TNF-α G-308A polymorphism and the risk for progression of IgA nephropathy in main analysis [23,24,25,26,27,28,29].

Figure 4

Forest plot of TNF-α G-308A polymorphism and the risk of sporadic IgA nephropathy in Caucasians [25,26,27].

Figure 5

Forest plot of TNF-α G-308A polymorphism and the risk of sporadic IgA nephropathy in Asians [23,24,28,29].

Figure 6

Forest plot of TNF-α G-308A polymorphism and the risk for progression of sporadic IgA nephropathy in Caucasians [25,26,27].

Figure 7

Forest plot of TNF-α G-308A polymorphism and the risk for progression of sporadic IgA nephropathy in Asians [23,24].