An intronic polymorphism of gene shows a risk association with biopsy-proven acute rejection in renal transplant recipients.

BACKGROUND

We aimed to explore the influence of single nucleotide polymorphisms (SNPs) in gene on the occurrence of biopsy-proven acute rejection (BPAR) in renal transplant recipients.

METHODS

Blood samples from 131 subjects with stable allograft function (STA) and 69 with BPAR episodes were collected and analyzed using target sequencing (TS) with an established panel. Odds ratios (OR) and 95% confidence intervals (95% CIs) were calculated for logistic regression models adjusted for confounding factors. Pathological changes were extracted and the relationship with tagger SNPs was calculated. Moreover, the CCK-8 assay was performed to explore the proliferation of T lymphocytes, and PCR, Western blotting and enzyme-linked immunosorbent assay were applied to identify the effect of mutant on the activation of T cells.

RESULTS

High-quality readouts were obtained for 55 SNPs and 14 tagger SNPs were remained for further analysis. After adjusting for clinical confounding factors, the distribution of four SNPs, including rs2290154, rs2304738, rs754093 and rs754096, were statistically significant between STA and BPAR groups. Pathological association analysis indicated one SNP, rs2290154, was significantly related with the Banff score and renal tubulitis. Our study suggested that rs2290154 mutant could remarkably promote the T cell proliferation, increase the transcription of mRNA and expression of NFATC1 protein, as well as the interleukin-2 (IL-2) secretion.

CONCLUSIONS

We reported the crucial association of gene with the occurrence of acute rejection (AR) episodes. Moreover, rs2290154 was significantly involved in the T lymphocytes activation and proliferation through increasing the translation of mRNA and expression of NFATC1 protein, along with the secretion of IL-2.