title: Association between granzyme B and perforin I polymorphisms and allograft outcomes in Hispanic kidney transplant recipients.
abstract: Granzyme B (GZMB) and perforin 1 gene (PRF1) are key effector molecules of cytotoxic T lymphocytes, in causing acute and chronic solid organ transplant rejection. In this study, we analyzed the impact of GZMB and PRF1 polymorphism on kidney allograft outcomes. In all, 527 de novo kidney Hispanic allograft recipients were genotyped for PRF1 (rs10999426, rs35947132) and GZMB (rs8192917, rs7144366). PRF1 (rs10999426, rs35947132) G alleles and GG genotypes were negatively associated with allograft rejection, demonstrating protection against allograft rejection (OR = 0.61, p = 0.005 for rs1099946; OR = 0.4, p = 0.01 for rs 35947132). On the other hand, the GA heterozygosity of PRF1 was found marginally associated with the rejection group (OR = 1.53, p = 0.05 for rs10999426; OR = 2.24, p = 0.07 for rs35947132). There was a significant increase in allograft survival in time period studied for the PRF1 (rs10999426) GG genotype, while the GA heterozygosity was associated with graft failure. We found no association for polymorphic markers in GZMB gene with allograft rejection. Survival was significantly improved for patients who were homozygous TT for the GZMB (rs8192917) (TT vs. CC/TT, p = 0.041). The result suggests that PRF1 and GZMB gene polymorphisms may determine the incidence of acute rejection or graft survival among Hispanic allograft recipients.
authors.affiliation: Nova Southeastern University, Miami, FL, USA.
authors.forename: Eglis
authors.initials: E
authors.lastname: Corrales-Tellez
authors.forename: Don
authors.initials: D
authors.lastname: Vu
authors.forename: Tariq
authors.initials: T
authors.lastname: Shah
authors.forename: Ian
authors.initials: I
authors.lastname: Hutchinson
authors.forename: David I
authors.initials: DI
authors.lastname: Min
mesh_terms: D000328:Adult; D064591:Allografts; D005260:Female; D005500:Follow-Up Studies; D005838:Genotype; D006084:Graft Rejection / Q000453:epidemiology / Q000235:genetics*; D006085:Graft Survival; D053804:Granzymes / Q000235:genetics*; D006630:Hispanic or Latino / Q000235:genetics*; D006801:Humans; D007674:Kidney Diseases / Q000235:genetics / Q000401:mortality* / Q000601:surgery; D016030:Kidney Transplantation / Q000401:mortality*; D008297:Male; D008875:Middle Aged; D054353:Perforin; D011110:Polymorphism, Genetic / Q000235:genetics*; D052899:Pore Forming Cytotoxic Proteins / Q000235:genetics*; D011379:Prognosis; D015996:Survival Rate
chemical_list: C510468:PRF1 protein, human; D052899:Pore Forming Cytotoxic Proteins; D054353:Perforin; C509213:GZMB protein, human; D053804:Granzymes