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

Abstract

Background: 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. 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-b1 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-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. Stratified analyses also associated TGF-b1 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-b1 and IL-4 genes including rs1800469, rs1800470, rs1800471, and rs8179190 may be important genetic contributors to CKD susceptibility.

Role of eNOS and TGFβ1 gene polymorphisms in the development of diabetic nephropathy in type 2 diabetic patients in South Indian population

“…They reported a highest OR of 4.16 (2.92-5.94) among the other studies, which was also comparatively very high than our study [28]. Another recent meta-analysis study by Mai et al, 2020 has also proved the association of TGFβ1 polymorphism (rs18000471) in the development of chronic kidney diseases [29].…”

Transforming growth factor-β1: relation between its single-nucleotide genetic variants and sickle cell nephropathy

“…A recent study suggested that genetic variants in the TGF-β1 and IL-4 genes rs1800469, rs1800470, rs1800471, and rs8179190 may play a role as a genetic contributor to the susceptibility of chronic kidney disease [10]. In addition, TGF β1 was found to induce renal hypertrophy and fibrosis [10].…”

“…It has three closely related isoforms TGF-β1, TGF-β2 and TGF-β3. TGF-β has dual effects, which are pro-inflammatory and anti-inflammatory, with a pronounced immunosuppressive effect [10]. TGF-β1, -β2, and -β3 share 71-80% sequence identity and signal through the same receptors [11].…”

“…It functions in autocrine and paracrine manners to regulate cell proliferation, differentiation, apoptosis, adhesion, immunity, and extracellular matrix (ECM) turnover in the kidneys. It has fibrogenic action through enhancing the production of extracellular matrix proteins [10]. Several genetic variants have been proved to affect TGF-β1 production and functions, such as (rs1800469), which is in the promoter region of TGF-β1 gene that can alter the rate of secretion of TGF-β1 and hence the circulating levels of mature TG-β1 [10], whereas the (rs1800471) was reported to affect the level of TGF-β1 as well as be associated with inter-individual variation in levels of the TGF-β1 production in vitro and with fibrosis in lung allografts [13,14].…”