Donor g protein beta 3 subunit 825TT genotype is associated with reduced kidney allograft survival

Recent studies have identified a novel polymorphism (C825T) of the gene enc oding the beta 3 subunit of heterotrimeric G proteins (G beta 3). associate d with enhanced activation of G proteins, which appears to be more common i n hypertensive patients. In the present study, the relationship between thi s genetic variant and kidney allograft survival was examined over the first 3 yr after transplantation, in 320 consecutive Caucasian patients recruite d from the Berlin-Steglitz transplantation center between 1988 and 1993. Cl inical parameters, transplantation data, and details of graft survival were retrieved from clinical records. After multivariate adjustment for covaria tes (Cox hazard regression), the G beta 3 825TT donor-genotype was associat ed with a significantly decreased graft survival representing a relative ri sk of graft loss of 2.2 (95% confidence interval, 1.1 to 4.8) compared to T C and CC grafts within the observation period. This association between don or TT genotype and graft survival remained stable even after stepwise exclu sion of covariates from the multivariate model. In contrast, there was no s ignificant relationship between recipient genotype and allograft function. These findings indicate that individuals receiving renal allografts from do nors homozygous for the G beta 3-825T allele may have an increased risk of developing allograft failure. Additional studies on the role of this geneti c marker as well as the role of pertussis toxin-sensitive G proteins in the development of chronic rejection appear warranted.