Donor genetic determinant of thymopoiesis, rs2204985, and stem cell transplantation outcome in a multipopulation cohort

Background: A genetic polymorphism, rs2204985, has been reported to be associated with the diversity of T-cell antigen receptor repertoire and TREC levels, reflecting the function of the thymus. As the thymus function can be assumed to be an important factor regulating the outcome of stem cell transplantation (SCT), it was of great interest that rs2204985 showed a genetic association to disease-free and overall survival in a German SCT donor cohort. Tools to predict the outcome of SCT more accurately would help in risk assessment and patient safety. Objective: To evaluate the general validity of the original genetic association found in the German cohort, we determined genetic associations between rs2204985 and the outcome of SCT in 1,473 SCT donors from four different populations. Study design: Genetic associations between rs2204985 genotype AA versus AG/GG and overall survival (OS) and disease-free survival (DFS) in 1,473 adult, allogeneic SCT from Finland, the United Kingdom, Spain, and Poland were performed using the Kaplan-Meier analysis and log-rank tests. We adjusted the survival models with covariates using Cox regression. Results: In unrelated SCT donors (N = 425), the OS of genotype AA versus AG/GG had a trend for a similar association (p = 0.049, log-rank test) as previously reported in the German cohort. The trend did not remain significant in the Cox regression analysis with covariates. No other associations were found. Conclusion: Weak support for the genetic association between rs2204985, previously also associated with thymus function, and the outcome of SCT could be found in a cohort from four populations.