title: Genetic predisposition of donors affects the allograft outcome in kidney transplantation; polymorphisms of stromal-derived factor-1 and CXC receptor 4.
abstract: Genetic interaction between donor and recipient may dictate the impending responses after transplantation. In this study, we evaluated the role of the genetic predispositions of stromal-derived factor-1 (SDF1) [rs1801157 (G>A)] and CXC receptor 4 (CXCR4) [rs2228014 (C>T)] on renal allograft outcomes. A total of 335 pairs of recipients and donors were enrolled. Biopsy-proven acute rejection (BPAR) and long-term graft survival were traced. Despite similar allele frequencies between donors and recipients, minor allele of SDF1 rs1801157 (GA+AA) from donor, not from recipients, has a protective effect on the development of BPAR compared to wild type donor (GG) (P  = 0.005). Adjustment for multiple covariates did not affect this result (odds ratio 0.39, 95% C.I 0.20-0.76, P = 0.006). CXCR4 rs2228014 polymorphisms from donor or recipient did not affect the incidence of acute rejection. SDF1 was differentially expressed in renal tubular epithelium with acute rejection according to genetic variations of donor rs1801157 showing higher expressions in the grafts from GG donors. Contrary to the development of BPAR, the presence of minor allele rs1801157 A, especially homozygocity, predisposed poor graft survival (P = 0.001). This association was significant after adjusting for several risk factors (hazard ratio 3.01; 95% C.I = 1.19-7.60; P = 0.020). The allelic variation of recipients, however, was not associated with graft loss. A donor-derived genetic polymorphism of SDF1 has influenced the graft outcome. Thus, the genetic predisposition of donor should be carefully considered in transplantation.
authors.affiliation: Seoul National University Kidney Research Institute, Seoul, Korea.
authors.forename: Jung Pyo
authors.initials: JP
authors.lastname: Lee
authors.forename: Jong Bin
authors.initials: JB
authors.lastname: Bae
authors.forename: Seung Hee
authors.initials: SH
authors.lastname: Yang
authors.forename: Ran-Hui
authors.initials: RH
authors.lastname: Cha
authors.forename: Eun Young
authors.initials: EY
authors.lastname: Seong
authors.forename: Yang Jin
authors.initials: YJ
authors.lastname: Park
authors.forename: Jongwon
authors.initials: J
authors.lastname: Ha
authors.forename: Myoung Hee
authors.initials: MH
authors.lastname: Park
authors.forename: Jin Ho
authors.initials: JH
authors.lastname: Paik
authors.forename: Yon Su
authors.initials: YS
authors.lastname: Kim
mesh_terms: D000328:Adult; D000483:Alleles; D054377:Chemokine CXCL12 / Q000235:genetics* / Q000502:physiology; D005260:Female; D020022:Genetic Predisposition to Disease; D006084:Graft Rejection / Q000235:genetics*; D006085:Graft Survival / Q000235:genetics; D006801:Humans; D016030:Kidney Transplantation / Q000502:physiology; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000502:physiology; D019718:Receptors, CXCR4 / Q000235:genetics* / Q000502:physiology; D014019:Tissue Donors; D014184:Transplantation, Homologous; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: C527276:CXCR4 protein, human; D054377:Chemokine CXCL12; D019718:Receptors, CXCR4