Ethnicity-Stratified Analysis of the Association between TNF-α Genetic Polymorphisms and Acute Kidney Injury: A Systematic Review and Meta-Analysis

Abstract

Background. Several studies have reported conflicting findings regarding the association between tumor necrosis factor-alpha (TNF-α) genetic polymorphisms and acute kidney injury (AKI). Therefore, we performed this meta-analysis to further investigate whether TNF-α variants are related to AKI susceptibility. Methods. A comprehensive search of observational studies on the association of TNF-α polymorphism with AKI susceptibility was conducted in the PubMed, Cochrane, and Embase databases through February 10, 2020. Pooled odds ratios (ORs) and 95% corresponding confidence intervals (95% CIs) were analyzed to evaluate the strength of the relationship. Results. A total of 8 studies involving 6694 patients (2559 cases and 4135 controls) were included. Pooled analysis showed a trend of increased risk between the TNF-α rs1800629 variant and AKI (A vs. G: $\text{OR}\left[95\%\text{CI}\right]=1.33\left[0.98‐1.81\right]$ ) among the overall population. Ethnicity-stratified analysis indicated that the TNF-α rs1800629 variant was a risk factor for Asians ( $\text{OR}\left[95\%\text{CI}\right]=1.93\left[1.59‐2.35\right]$ ) while it is not for Caucasians ( $\text{OR}\left[95\%\text{CI}\right]=1.04\left[0.91‐1.20\right]$ ). Additionally, we also found that TNF-α rs1799964 polymorphism was observed to have a significant relationship with AKI risk in Asian patients (C vs. T, $\text{OR}\left[95\%\text{CI}\right]=1.26\left[1.11‐1.43\right]$ ). Conclusions. The TNF rs1800629 polymorphism exhibited a trend toward AKI susceptibility with ethnic differences. The relationship was found to be significant among the Asian population, but not among those of Caucasian origin. Additionally, the TNF-α rs1799964 polymorphism was also related to a significantly increased risk of AKI in Asians.