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

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: OR [95%CI] = 1.33 [0.98‐1.81]) among the overall population. Ethnicity-stratified analysis indicated that the TNF-α rs1800629 variant was a risk factor for Asians (OR [95%CI] = 1.93 [1.59‐2.35]) while it is not for Caucasians (OR [95%CI] = 1.04 [0.91‐1.20]). 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, OR [95%CI] = 1.26 [1.11‐1.43]). 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.