title: Systematic assessment of the influence of complement gene polymorphisms on kidney transplant outcome.
abstract: 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.
authors.affiliation: Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne NE2 4HH, UK. Electronic address: luca.ermini@yahoo.co.uk.
authors.forename: Luca
authors.initials: L
authors.lastname: Ermini
authors.affiliation: Department of Medical and Molecular Genetics, King's College, London SE1 9RT, UK. Electronic address: michael.weale@kcl.ac.uk.
authors.forename: Michael E
authors.initials: ME
authors.lastname: Weale
authors.affiliation: MRC Centre for Transplantation, King's College, London SE1 9RT, UK. Electronic address: katherine.brown@kcl.ac.uk.
authors.forename: Katherine M
authors.initials: KM
authors.lastname: Brown
authors.affiliation: Department of Medical and Molecular Genetics, King's College, London SE1 9RT, UK. Electronic address: irene.rebollo_mesa@kcl.ac.uk.
authors.forename: Irene Rebollo
authors.initials: IR
authors.lastname: Mesa
authors.affiliation: NHS Blood and Transplant, Newcastle upon Tyne, UK. Electronic address: Martin.Howell@nhsbt.nhs.uk.
authors.forename: W Martin
authors.initials: WM
authors.lastname: Howell
authors.affiliation: Clinical Transplantation Laboratory, GSTS Pathology, Guy's Hospital, London SE1 9RT, UK. Electronic address: robert.vaughan@kcl.ac.uk.
authors.forename: Robert
authors.initials: R
authors.lastname: Vaughan
authors.affiliation: MRC Centre for Transplantation, King's College, London SE1 9RT, UK. Electronic address: paramit.chowdhury@gstt.nhs.uk.
authors.forename: Paramit
authors.initials: P
authors.lastname: Chowdhury
authors.affiliation: MRC Centre for Transplantation, King's College, London SE1 9RT, UK. Electronic address: steven.sacks@kcl.ac.uk.
authors.forename: Steven H
authors.initials: SH
authors.lastname: Sacks
authors.affiliation: Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne NE2 4HH, UK. Electronic address: neil.sheerin@ncl.ac.uk.
authors.forename: Neil S
authors.initials: NS
authors.lastname: Sheerin
mesh_terms: D015331:Cohort Studies; D003165:Complement System Proteins / Q000235:genetics*; D003404:Creatinine / Q000097:blood; D015870:Gene Expression; D055106:Genome-Wide Association Study; D005838:Genotype; D006084:Graft Rejection / Q000097:blood / Q000175:diagnosis / Q000235:genetics* / Q000276:immunology; D006085:Graft Survival / Q000276:immunology; D006801:Humans; D007668:Kidney / Q000276:immunology / Q000378:metabolism / Q000473:pathology / Q000601:surgery; D016030:Kidney Transplantation; D037601:Mannose-Binding Lectin / Q000235:genetics* / Q000276:immunology; D020641:Polymorphism, Single Nucleotide; D051436:Renal Insufficiency, Chronic / Q000097:blood / Q000235:genetics* / Q000276:immunology / Q000601:surgery; D014019:Tissue Donors; D066027:Transplant Recipients; D016896:Treatment Outcome
chemical_list: D037601:Mannose-Binding Lectin; D003165:Complement System Proteins; D003404:Creatinine
keywords: Complement; Kidney transplantation; Outcome; Single nucleotide polymorphism