The importance of antibody-mediated rejection (ABMR) on the renal transplant recipients has been recognized in recent years. However, the pathogenesis of ABMR following kidney transplantation still remained unclear. We aimed to investigate the influence of X-ray repair cross-complementing group (XRCC) genes, including XRCC1 and XRCC4-7, on the development of ABMR in renal transplant recipients.

A total of 200 renal transplant recipients in our transplant center were enrolled, and their blood samples were collected. Then, DNA samples were extracted from blood samples, and whole-exome sequencing (WES) based on the next-generation sequencing was used to test the single nucleotide polymorphisms (SNPs) on the XRCC1, XRCC4, XRCC5, XRCC6 and XRCC7. The HaploView software was used to test the minor allele frequencies (MAF) and to perform the Hardy-Weinberg equilibrium (HWE) and linkage disequilibrium (LD) analysis. Significant SNPs were explored with the logistic regression model adjusted by age, gender and immunosuppressive protocol. Moreover, significant clinical variables and haplotypes were identified by the linear multivariable regression and general linear model (GLM) in SPSS software.

A total of 102 SNPs were identified by WES, and 27 SNPs were selected with MAF>0.05 and HWE>0.05. The logistic regression model identified 6 significant SNPs in Addictive model on XRCC5 gene, and 3 significant SNPs on XRCC5 genes and one significant SNP on XRCC4 gene in HET model after adjusted by age, gender and immunosuppressive protocol. Immunosuppressive protocol and the administration of sirolimus were found to significantly influence the development of ABMR after kidney transplantation. Moreover, four haplotypes were recognized by LD analysis, and no haplotype were observed to be significantly associated with the ABMR by GLM model.

In conclusion, we identified 8 significant SNPs on XRCC4 and XRCC5 SNPs which were involved in the pathogenesis of ABMR. Immunosuppressive protocol and the administration of sirolimus were remarkably related with ABMR after kidney transplantation. Our conclusions suggested the essential role of XRCC4 and XRCC5 genes during the ABMR following kidney transplantation.

CITATION INFORMATION: Wang Z., Han Z., Tao J., Tan R., Gu M. Influence of X-Ray Repair Cross-Complementing Group (XRCC) Genes Polymorphisms on the Development of Antibody-Mediated Rejection (ABMR) in Renal Transplant Recipients Am J Transplant. 2017;17 (suppl 3).

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