Associatin Of Complement Component 3 Single Nucleotide Polymorphisms With Antibody-Mediated Rejection After Kidney Transplantation: A Single-Center Experience

Background: Antibody-mediated rejection(ABMR)is an important risk of allograft dysfunction in kidney transplantation.The complement component 3 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.Methods and materials: Blood samples of 199 renal transplant recipients containing 68 with ABMR and 131 with stable graft function were collected,and analyzed by targer sequencing based on technology of next-generation sequencing with an established gene panel.Results: High quality readout was obtained in 116 C3 SNPs.29 tagger SNPs were remained for association analysis by the analysis of HWE and linkage disequilibrium.After being adjusted with age,sex and immunosuppressive protocols,five tagger SNPs were found to be significantly associated with the pathogenesis of ABMR among various model(rs10411506:dominant model:OR 2.73,95% CI:1.16-6.68,P = 0.028;HET model:OR 3.05,95% CI:1.22-7.64,P = 0.017;rs2230205:dominant model:OR 2.52,95% CI:1.07-5.92,P = 0.034;rs2230201:OR 2.41,95% CI:1.03-5.64,P = 0.042;rs2230201:HET model:OR 2.41,95% CI:1.03-5.64,P = 0.042;rs408290:HET model:OR 2.91,95% CI:1.19-7.16,P = 0.020;Chr19:6692790:HET model:OR 2.76,95% CI:1.21-6.28,P = 0.016).The linkage analysis showed relatively low linkage disequilibrium among three tagger SNPs(rs10411506?rs2230201 and rs2230205).In addition,no significant correlation was found between other C3 tagger SNPs or 5 haplotype blocks,and the development of ABMR.Conclusions: Our study firstly identified the five tagger SNPs(rs10411506,rs2230205,rs2230201,rs408290 and Chr19:6692790)in C3 gene were statistically correlated with the pathogenesis of ABMR after kidney transplantation.No significant correlation was found between other C3 tagger SNPs or 5 haplotype blocks,and the development of ABMR.These findings may have implications for the treatment and prevention of ABMR.