Thymopoiesis-regulating genetic variant rs2204985 affects outcome of liver but not kidney transplantation

The genetic variant rs2204985 at the T‑cell antigen receptor locus has been associated with regulation of thymopoiesis and outcome in hematopoietic stem cell transplantation. We investigated the association of this variant with outcomes of liver and kidney transplantation. We assessed the association of rs2204985 with post-transplantation outcomes in two Finnish cohorts comprising 666 liver and 1,025 kidney transplantations using adjusted logistic regression and Cox models. Findings from the Finnish liver transplant cohort were validated in an independent Dutch replication cohort of 618 liver transplantations. In the Finnish liver transplant cohort, the donor rs2204985*GG genotype was associated with lower overall survival (multivariable Cox regression, hazard ratio = 1.54, 95% confidence interval [CI] = 1.02–2.34, p = 0.041). In the Dutch cohort, the donor GG genotype increased the risk of graft loss (OR = 1.47, 95% CI = 0.99–2.21, p = 0.059) but not mortality (OR = 1.00, 95% CI = 0.66–1.51, p = 0.981). In the meta-analysis of the Finnish and Dutch liver transplant cohorts the donor rs2204985*GG genotype was associated with graft loss (OR = 1.42, 95% CI = 1.06–1.90, p = 0.019). These results indicate that the genetic variant rs2204985*GG regulating thymopoiesis may affect liver transplantation outcome. Although our study provides no mechanistic clues to the association, the findings emphasize the immunological role of the liver.