Donor G protein beta3 subunit 825TT genotype is associated with reduced kidney allograft survival

Recent studies have identified a novel polymorphism (C825T) of the gene encoding the beta3 subunit of heterotrimeric G proteins (Gbeta3), associated with enhanced activation of G proteins, which appears to be more common in hypertensive patients. In the present study, the relationship between this genetic variant and kidney allograft survival was examined over the first 3 yr after transplantation, in 320 consecutive Caucasian patients recruited from the Berlin-Steglitz transplantation center between 1988 and 1993. Clinical parameters, transplantation data, and details of graft survival were retrieved from clinical records. After multivariate adjustment for covariates (Cox hazard regression), the Gbeta3 825TT donor-genotype was associated with a significantly decreased graft survival representing a relative risk of graft loss of 2.2 (95% confidence interval, 1.1 to 4.8) compared to TC and CC grafts within the observation period. This association between donor TT genotype and graft survival remained stable even after stepwise exclusion of covariates from the multivariate model. In contrast, there was no significant relationship between recipient genotype and allograft function. These findings indicate that individuals receiving renal allografts from donors homozygous for the Gbeta3-825T allele may have an increased risk of developing allograft failure. Additional studies on the role of this genetic marker as well as the role of pertussis toxin-sensitive G proteins in the development of chronic rejection appear warranted.