Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea.
Nephrol Dial Transplant. 2011 Oct;26(10):3378-85. doi: 10.1093/ndt/gfr025. Epub 2011 Mar 10.
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. We investigated the impacts of genetic variations in C5 and its receptor (C5aR) of both recipients and donors on renal allograft outcomes.
Seven single-nucleotide polymorphisms (SNPs) in C5 (rs12237774, rs2159776, rs17611, rs25681, rs2241004, rs10985126 and 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.
Three C5 SNPs (rs2159776, rs17611 and rs25681) in recipients had a tendency toward a reduced glomerular filtration rate at 1 year after transplantation. There were four haplotypes in the H2 linkage disequilibrium block, which was formed by four SNPs (rs2159776, rs17611, rs25681 and rs2241004). The GGCG haplotype in both recipients and donors was associated with lower glomerular filtration rate at 1 year (60.9 ± 15.9 versus 66.4 ± 15.5 mL/min/1.73 m(2), P = 0.020; 60.6 ± 15.3 versus 66.2 ± 15.8 mL/min/1.73 m(2), 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 (logrank test, P = 0.024). However, C5 polymorphisms were not correlated with serum C5 level. C5aR polymorphism had no significant impact on the allograft outcomes.
The GGCG haplotype of C5 in both recipients and donors was associated with lower renal allograft function.
补体在移植后的排斥反应和缺血再灌注损伤中都起着重要作用。补体 5（C5）是一种关键的补体，它启动膜攻击复合物的组装，并介导各种免疫细胞的趋化作用。我们研究了受体和供体中 C5 及其受体（C5aR）的遗传变异对肾移植结局的影响。
在 191 对受体-供体对中，对 C5 中的 7 个单核苷酸多态性（SNP）（rs12237774、rs2159776、rs17611、rs25681、rs2241004、rs10985126 和 rs10818500）和 C5aR 基因中的一个 SNP（rs10404456）进行了基因分型。确定了多态性与移植物结局的关联。
受者中 3 个 C5SNP（rs2159776、rs17611 和 rs25681）在移植后 1 年时肾小球滤过率有降低的趋势。在由 4 个 SNP（rs2159776、rs17611、rs25681 和 rs2241004）形成的 H2 连锁不平衡块中存在 4 个单倍型。供体和受者中的 GGCG 单倍型与 1 年时的肾小球滤过率较低相关（60.9±15.9 与 66.4±15.5 mL/min/1.73 m(2)，P=0.020；60.6±15.3 与 66.2±15.8 mL/min/1.73 m(2)，P=0.017）。这种关联在移植后 7 年仍持续存在（受者 P=0.015；供者 P=0.039）。受者中 GGCG 单倍型的存在与移植物存活率较差相关（logrank 检验，P=0.024）。然而，C5 多态性与血清 C5 水平无明显相关性。C5aR 多态性对移植物结局无显著影响。
供体和受者中 C5 的 GGCG 单倍型与较低的肾移植功能相关。
