Abstract
BackgroundAnti-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.MethodsA 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.ResultsNineteen 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.ConclusionsAvailable 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.
Highlights
Chronic kidney disease (CKD) is defined as the presence of kidney damage or a decreased glomerular filtration rate (GFR) of less than 60 ml/min/1.73 m2 for at least 3 months (Webster et al, 2017)
The pooled analysis showed that transforming growth factor-b1 (TGF-b1) rs1800469 was associated with decreased susceptibility to CKD (CC + TC vs. TT, odds ratios (ORs) = 0.33, 95% confidence intervals (CIs): 0.15–0.76, P = 0.009; CC vs. TT, OR = 0.33, 95% CI: 0.15–0.73, P = 0.006), whereas TGF-b1 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-b1 rs1800469 was associated with CKD susceptibility in Asians and Caucasians, and there was an association of TGF-b1 rs1800470 and IL-4 rs8179190 with CKD in Asians
Summary
Chronic kidney disease (CKD) is defined as the presence of kidney damage or a decreased glomerular filtration rate (GFR) of less than 60 ml/min/1.73 m2 for at least 3 months (Webster et al, 2017). In Europe, about 70 million people are affected with CKD, and the prevalence of RRT has grown by almost 50% over the past decade (Vanholder et al, 2017). In the Chronic Renal Insufficiency Cohort (CRIC) study, biomarkers of inflammation were inversely associated with measures of kidney function and positively with albuminuria in CKD patients (Gupta et al, 2012). There has been a growing interest in the association between CKD and anti-inflammatory cytokines including transforming growth factor-b1 (TGF-b1), interleukin-4 (IL-4), and IL-10. Anti-inflammatory cytokine polymorphisms in the transforming growth factor-b1 (TGF-b1), 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
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