Clinical impact of glucocorticoid responsiveness-related gene polymorphism on graft-versus-host disease and survival after single-unit cord blood transplantation

Graft-versus-host disease (GVHD) is a major complication after allogeneic hematopoietic cell transplantation (HCT), and glucocorticoids remain the standard first-line treatment. However, glucocorticoid responses vary widely and are influenced by genetic polymorphisms in glucocorticoid signaling pathways. Their impact after cord blood transplantation (CBT) is unclear. We retrospectively analyzed adult patients who underwent single-unit CBT at our institution between 2005 and 2023 with available donor or recipient DNA. Genotyping of NR3C1 (rs33388) and GLCCI1 (rs37972, rs37973) was performed using TaqMan® assays. In univariate analyses, donor GLCCI1 rs37973 AG/AA genotypes were associated with a higher incidence of grades II to IV acute GVHD but a lower incidence of chronic GVHD compared with GG donors. Multivariate analysis confirmed that GLCCI1 rs37973 AG/AA donors had a significantly reduced risk of chronic GVHD (hazard ratio 0.57, 95% confidence interval 0.35-0.93, P = 0.025). Among 30 patients who developed grades III to IV acute GVHD treated with glucocorticoids, recipient NR3C1 rs33388 TT genotype was associated with significantly lower overall survival compared with AT/AA (24.4% vs. 63.5% at 5 years, P = 0.044). These findings suggest that donor GLCCI1 rs37973 and recipient NR3C1 rs33388 polymorphisms may influence GVHD risk and survival after CBT.