Impact of complement component 3/4/5 single nucleotide polymorphisms on renal transplant recipients with antibody-mediated rejection

Abstract

Antibody-mediated rejection (ABMR) is an important risk of allograft dysfunction in kidney transplantation. The complement system is considered to be associated with the generation of alloreative antibodies and donor-specific antibodies. However, the association of complement single nucleotide polymorphisms (SNPs) with ABMR still remained unclear. Blood samples of 199 renal transplant recipients containing 68 with ABMR and 131 with stable graft function were collected, and analyzed by next-generation sequencing with an established gene panel. High quality readout was obtained in 18 C3 SNPs, 9 C4 SNPs and 22 C5 SNPs. Concerning C3 gene polymorphisms, after being adjusted with age, sex and immunosuppressive protocols, rs10411506 and rs2230205 were found to be statistically associated with ABMR in dominant model (rs10411506: OR=2.73, 95% CIs: 1.16, 6.68, P=0.028; rs2230205: OR=2.52, 95% CIs: 1.07, 5.92, P=0.034); rs10411506, rs2230205 and rs2230201 were found different in HET model (rs10411506: OR=3.05, 95% CIs: 1.22, 7.64, P=0.017; rs2230205: OR=2.90, 95% CIs: 1.20, 7.00, P=0.018; rs2230201: OR=2.41, 95% CIs: 1.03, 5.64, P=0.042). The linkage analysis showed relatively high linkage disequilibrium among these SNPs. In addition, no significant correlation was found between C4 SNPs, or C5 SNPs, and the development of ABMR. Our study firstly identified the two SNPs (rs10411506 and rs2230205) in C3 gene were statistically correlated with ABMR in kidney transplantation. These findings may have implications for the diagnosis and prevention of ABMR.