title: Genotypic diversity of complement component C4 does not predict kidney transplant outcome.
abstract: Gene copy number of complement component C4, which varies among individuals, may determine the intrinsic strength of the classical complement pathway. Presuming a major role of complement as an effector in transplant rejection, we hypothesized that C4 genetic diversity may partially explain the variation in allograft outcomes. This retrospective study included 1969 deceased-donor kidney transplants randomly selected from the Collaborative Transplant Study DNA bank. We determined recipient and donor gene copy number of total C4, C4 isotypes (C4A and C4B), and C4 gene length variants (C4L and C4S) by quantitative real-time PCR analysis. Groups defined according to recipient C4 gene copy number (low, intermediate, and high) had similar 10-year allograft survival. Genotypic groups showed comparable rates of graft dysfunction, treatment for rejection, immunological graft loss, hospitalization for infection, malignant disease, and death. Similarly, separate analyses of C4A, C4B, C4L, and C4S; combined evaluation of donor and recipient C4 genotype; or analysis of recipients with higher risk for rejection did not reveal considerable outcome effects. In conclusion, we did not demonstrate that C4 gene copy number associates with transplant outcome, and we found no evidence that the resulting variation in the strength of classical complement activation influences susceptibility to rejection.
authors.affiliation: Division of Nephrology and Dialysis, Department of Medicine III, Medical University of Vienna, Währinger Gürtel 18-20, A-1090 Vienna, Austria.
authors.forename: Markus
authors.initials: M
authors.lastname: Wahrmann
authors.forename: Bernd
authors.initials: B
authors.lastname: Döhler
authors.forename: Andrea
authors.initials: A
authors.lastname: Ruhenstroth
authors.forename: Helmuth
authors.initials: H
authors.lastname: Haslacher
authors.forename: Thomas
authors.initials: T
authors.lastname: Perkmann
authors.forename: Markus
authors.initials: M
authors.lastname: Exner
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Rees
authors.forename: Georg A
authors.initials: GA
authors.lastname: Böhmig
mesh_terms: D000328:Adult; D000368:Aged; D003181:Complement C4 / Q000235:genetics*; D005260:Female; D018628:Gene Dosage; D014644:Genetic Variation; D005838:Genotype; D006084:Graft Rejection / Q000235:genetics; D006801:Humans; D016030:Kidney Transplantation; D008297:Male; D008875:Middle Aged; D014184:Transplantation, Homologous; D016896:Treatment Outcome
chemical_list: D003181:Complement C4