Systematic assessment of the influence of complement gene polymorphisms on kidney transplant outcome

TY - JOUR

T1 - Systematic assessment of the influence of complement gene polymorphisms on kidney transplant outcome

AU - Ermini, Luca

AU - Weale, Michael E.

AU - Brown, Katherine M.

AU - Mesa, Irene Rebollo

AU - Howell, W. Martin

AU - Vaughan, Robert

AU - Chowdhury, Paramit

AU - Sacks, Steven H.

AU - Sheerin, Neil S.

PY - 2016/4

Y1 - 2016/4

N2 - The importance of the innate immune system, including complement, in causing transplant injury and augmenting adaptive immune responses is increasingly recognized. Therefore variability in graft outcome may in part be due to genetic polymorphism in genes encoding proteins of the immune system. This study assessed the relationship between single nucleotide polymorphisms (SNPs) in complement genes and outcome after transplantation. Analysis was performed on two patient cohorts of 650 and 520 transplant recipients. 505 tagged SNPs in 47 genes were typed in both donor and recipient. The relationships between SNPs and graft survival, serum creatinine, delayed graft function and acute rejection were analyzed. One recipient SNP in the gene encoding mannose binding lectin was associated with graft outcome after correction for analysis of multiple SNPs (p =6.41×10-5). When further correction was applied to account for analysis of the effect of SNPs in both donor and recipient this lost significance. Despite association p values of <0.001 no SNP was significantly associated with clinical phenotypes after Bonferroni correction. In conclusion, the variability seen in transplant outcome in this patient cohort cannot be explained by variation in complement genes. If causal genetic effects exist in these genes, they are too small to be detected by this study.

AB - The importance of the innate immune system, including complement, in causing transplant injury and augmenting adaptive immune responses is increasingly recognized. Therefore variability in graft outcome may in part be due to genetic polymorphism in genes encoding proteins of the immune system. This study assessed the relationship between single nucleotide polymorphisms (SNPs) in complement genes and outcome after transplantation. Analysis was performed on two patient cohorts of 650 and 520 transplant recipients. 505 tagged SNPs in 47 genes were typed in both donor and recipient. The relationships between SNPs and graft survival, serum creatinine, delayed graft function and acute rejection were analyzed. One recipient SNP in the gene encoding mannose binding lectin was associated with graft outcome after correction for analysis of multiple SNPs (p =6.41×10-5). When further correction was applied to account for analysis of the effect of SNPs in both donor and recipient this lost significance. Despite association p values of <0.001 no SNP was significantly associated with clinical phenotypes after Bonferroni correction. In conclusion, the variability seen in transplant outcome in this patient cohort cannot be explained by variation in complement genes. If causal genetic effects exist in these genes, they are too small to be detected by this study.

KW - Complement

KW - Kidney transplantation

KW - Outcome

KW - Single nucleotide polymorphism

UR - http://www.scopus.com/inward/record.url?scp=84954271212&partnerID=8YFLogxK

U2 - 10.1016/j.imbio.2015.12.006

DO - 10.1016/j.imbio.2015.12.006

M3 - Article

AN - SCOPUS:84954271212

SN - 0171-2985

VL - 221

SP - 528

EP - 534

JO - Immunobiology

JF - Immunobiology

IS - 4

ER -