Association of TGF-β1, IL-4, and IL-10 Polymorphisms With Chronic Kidney Disease Susceptibility: A Meta-Analysis

BACKGROUND: Anti-inflammatory cytokine polymorphisms in the transforming growth factor-β1 (TGF-β1), interleukin-4 (IL-4), and IL-10 genes have been implicated as risk factors for chronic kidney disease (CKD), but the results from published studies are inconsistent. Our meta-analysis reviews and summarizes the cumulative evidence for these associations. METHODS: A systematic literature search of five databases was performed up to October 2019. Two authors independently extracted data and evaluated the quality of included studies. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were generated from random-effects or fixed-effects models using Stata 12.0. RESULTS: Nineteen studies from 10 countries satisfied our inclusion criteria and were included in the meta-analysis. Overall, the pooled analysis showed that TGF-β1 rs1800469 was associated with decreased susceptibility to CKD (CC + TC vs. TT, OR = 0.33, 95% CI: 0.15–0.76, P = 0.009; CC vs. TT, OR = 0.33, 95% CI: 0.15–0.73, P = 0.006), whereas TGF-β1 rs1800471 was associated with increased CKD susceptibility (CC vs. CG + GG, OR = 1.68, 95% CI: 1.02–2.77, P = 0.041). In stratified analyses based on ethnicity, TGF-β1 rs1800469 was associated with CKD susceptibility in Asians and Caucasians, and there was an association of TGF-β1 rs1800470 and IL-4 rs8179190 with CKD in Asians. Stratified analyses also associated TGF-β1 rs1800471 with CKD susceptibility in Caucasians. Neither overall meta-analyses nor stratified analyses identified an association of the IL-10 rs1800869 and rs1800871 polymorphisms with susceptibility to CKD. CONCLUSIONS: Available data suggest that common polymorphisms in the TGF-β1 and IL-4 genes including rs1800469, rs1800470, rs1800471, and rs8179190 may be important genetic contributors to CKD susceptibility.