Association between TGFB1 genetic polymorphisms and chronic allograft dysfunction: a systematic review and meta-analysis

BACKGROUND: Epidemiological studies have investigated the role of transforming growth factor-β1 (TGF-β1) in chronic allograft dysfunction (CAD) following kidney transplantation. TGFB1 gene polymorphisms (SNP rs1800470 and rs1800471) may be associated with the risk of CAD. In this meta-analysis, the relationship between these two variations and the risk of CAD was explored. MATERIALS AND METHODS: MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials (CENTRAL), Embase, the Chinese CNKI and WANFANG databases were searched. Data were extracted and pooled results were estimated from odds ratios (ORs) with 95% confidential intervals (95% CIs). Quality assessments were performed, and publication bias of all eligible studies examined. RESULTS: Eight studies with 1038 subjects were included in our analysis. According to the effects on TGF-β1 secretion, haplotypes were categorized as “HIGH”, “INTERMEDIATE” and “LOW”. The combined results showed a statistically significant difference of TGFB1 haplotypes between the CAD recipients and control subjects when “HIGH” with “INTERMEDIATE” and “LOW” (“HIGH” vs. “INTERMEDIATE” + “LOW”: OR: 3.56, 95% CIs: 2.20, 5.78, P < 0.001) were compared. No significant association was found between the TGFB1 codon 10 or codon 25 and the CAD risk in all five genetic models. CONCLUSIONS: Our meta-analysis has found the haplotype of TGFB1 codon 10/25 T/T G/G and T/C G/G genotypes, associated with increased production of TGF-β1, was linked with CAD risk following kidney transplantation. Moreover, no significant difference was found between TGFB1 codon 10 or codon 25 and the development of CAD.