Association of complement 5 genetic polymorphism with renal allograft outcomes

Abstract

Background: Complements play important roles in both rejection and ischemia-reperfusion injury after transplantation. Complement 5 (C5) is a pivotal complement, which initiates the assembly of the membrane attack complex, and mediates chemotaxis of various immune cells. I investigated the impacts of genetic variations in C5 and its receptor (C5aR) of both recipients and donors on renal allograft outcomes. Materials and Methods: Seven single nucleotide polymorphisms (SNPs) in C5 (rs12237774

rs2159776

rs17611

rs25681

rs2241004

rs10985126

rs10818500) and one SNP (rs10404456) in the C5aR gene were genotyped in 191 recipient-donor pairs. The association of the polymorphisms with allograft outcomes was determined. Results: Three C5 SNPs (rs2159776

rs25681) in recipients had a tendency toward a reduced glomerular filtration rate (eGFR) at one year after transplantation. There were four haplotypes in the H2 linkage disequilibrium block, which was formed by four SNPs (rs2159776

rs2241004). The GGCG haplotype in both recipients and donors was associated with lower GFR at one year (60.9±15.9 vs. 66.4±15.5 ml/minute/1.73m2, P=0.020

60.6±15.3 vs. 66.2±15.8 ml/minute/1.73m2, P=0.017). The association was sustained over 7 years after transplantation (P=0.015 in recipients

P=0.039 in donors). The presence of the GGCG haplotype in recipients was associated with poorer graft survival (log-rank test, P=0.024). However, C5 polymorphisms were not correlated with serum C5 level. C5aR polymorphism had no significant impact on the allograft outcomes. Conclusions: The GGCG haplotype of complement 5 in both recipients and donors was associated with lower renal allograft function.