Association of complement 5 genetic polymorphism with renal allograft outcomes in Korea.

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. We investigated the impacts of genetic variations in C5 and its receptor (C5aR) of both recipients and donors on renal allograft outcomes.

METHODS:

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.

RESULTS:

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.

CONCLUSIONS:

The GGCG haplotype of C5 in both recipients and donors was associated with lower renal allograft function.

• Authors: Jong Cheol Jeong, Young-Hwan Hwang, Hyosang Kim, Han Ro, Hayne Cho Park, Yoon Jung Kim, Myung-Gyu Kim, Jongwon Ha, Myoung Hee Park, Dong Wan Chae, Curie Ahn, Jaeseok Yang
• Journal: Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association (Nephrol Dial Transplant) Vol. 26 Issue 10 Pg. 3378-85 (Oct 2011) ISSN: 1460-2385 [Electronic] England
• PMID: 21393613 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Complement C5
• Receptor, Anaphylatoxin C5a

Topics

• Adolescent
• Adult
• Complement C5 (genetics)
• Female
• Genotype
• Glomerular Filtration Rate
• Graft Rejection (genetics)
• Graft Survival (genetics)
• Haplotypes (genetics)
• Humans
• Kidney Diseases (genetics, therapy)
• Kidney Transplantation
• Linkage Disequilibrium
• Male
• Polymorphism, Single Nucleotide (genetics)
• Receptor, Anaphylatoxin C5a (genetics)
• Republic of Korea
• Transplantation, Homologous
• Young Adult