A Single-Nucleotide Polymorphism (rs1131243) of the Transforming Growth Factor Beta Signaling Pathway Contributes to Risk of Acute Rejection in Chinese Renal Transplant Recipients
Ming Zheng, Haiwei Yang, Wencheng Li, Jiajun Zhou, Jintao Wei, Zijie Wang, Miao Guo, Hao Chen, Li Sun, Zhijian Han, Jun Tao, Xiaobing Ju, Ruoyun Tan, Jifu Wei, Min Gu
Department of Urology, Nanjing Medical University First Affiliated Hospital, Nanjing, Jiangsu, China (mainland)
Med Sci Monit 2019; 25:9138-9158
Acute rejection (AR) is a common complication of kidney transplantation. The transforming growth factor beta (TGF-ß) signaling pathway has been observed to be involved in several cellular functions. Our study aimed to investigate the correlations between single-nucleotide polymorphisms (SNPs) in TGF-ß-related genes and the risk of AR in renal transplant recipients.
MATERIAL AND METHODS: This retrospective, single-center study included 200 Chinese renal transplant recipients. All exons, exon/intron boundaries, and flanking regions of the TGF-ß signaling pathway were detected by targeting sequencing (TS) based on next-generation sequencing technology. Tagger SNPs and haplotypes were identified after adjustment. A general linear model (GLM) was used to explore the confounding effect of clinical variables. Five adjusted inheritance models were utilized to investigate the influence of SNPs on AR, and Banff score was applied to evaluate the effect of related SNPs on pathological changes.
RESULTS: A total of 188 SNPs on TGF-ß genes were detected. Analysis of adjustment led to identification of 31 tagger SNPs and 10 haplotype blocks. After the analysis of a general linear model and 5 sirolimus-adjusted multiple inheritance models, 1 of the SNPs - rs1131243 on the TGF-ßR3 gene - was observed to be significantly associated with the occurrence of AR. Based on Banff score, no significant association was observed between SNPs and pathological changes.
CONCLUSIONS: In this study, we observed that the SNP rs1131243 on the TGF-ßR3 gene was significantly associated with the occurrence of AR in Chinese renal transplant recipients.
Keywords: Kidney Transplantation, Polymorphism, Single Nucleotide, Transforming Growth Factor beta