Uppugunduri, C. R. S. and Curtis, P. Huezo-Diaz and Nava, T. and Rezgui, M. A. and Mlakar, V and Mlakar, S. Jurkovic and Waespe, N. and Theoret, Y. and Gumy-Pause, F. and Bernard, F. and Chalandon, Y. and Boelens, J. J. and Bredius, R. G. M. and Dalle, J. H. and Nath, C. and Corbacioglu, S. and Peters, C. and Bader, P. and Shaw, P. and Bittencourt, H. and Krajinovic, M. and Ansari, Marc (2022) Association study of candidate DNA-repair gene variants and acute graft versus host disease in pediatric patients receiving allogeneic hematopoietic stem-cell transplantation. PHARMACOGENOMICS JOURNAL, 22 (1). pp. 9-18. ISSN 1470-269X, 1473-1150
Full text not available from this repository. (Request a copy)Abstract
Acute Graft versus Host Disease (aGvHD) grades 2-4 occurs in 15-60% of pediatric patients undergoing allogeneic haematopoietic stem-cell transplantation (allo-HSCT). The collateral damage to normal tissue by conditioning regimens administered prior to allo-HSCT serve as an initial trigger for aGvHD. DNA-repair mechanisms may play an important role in mitigating this initial damage, and so the variants in corresponding DNA-repair protein-coding genes via affecting their quantity and/or function. We explored 51 variants within 17 DNA-repair genes for their association with aGvHD grades 2-4 in 60 pediatric patients. The cumulative incidence of aGvHD 2-4 was 12% (n = 7) in the exploratory cohort. MGMT rs10764881 (G>A) and EXO rs9350 (c.2270C>T) variants were associated with aGvHD 2-4 [Odds ratios = 14.8 (0 events out of 40 in rs10764881 GG group) and 11.5 (95% CI: 2.3-191.8), respectively, multiple testing corrected p <= 0.001]. Upon evaluation in an extended cohort (n = 182) with an incidence of aGvHD 2-4 of 22% (n = 40), only MGMT rs10764881 (G>A) remained significant (adjusted HR = 2.05 [95% CI: 1.06-3.94]; p = 0.03) in the presence of other clinical risk factors. Higher MGMT expression was seen in GG carriers for rs10764881 and was associated with higher IC50 of Busulfan in lymphoblastoid cells. MGMT rs10764881 carrier status could predict aGvHD occurrence in pediatric patients undergoing allo-HSCT.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | GLUTATHIONE-S-TRANSFERASE; PROMOTER METHYLATION; MGMT; GVHD; POLYMORPHISM; MODULATION; EXPRESSION; BUSULFAN; OUTCOMES; DAMAGE; |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Abteilung für Pädiatrische Hämatologie, Onkologie und Stammzelltransplantation |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 27 Sep 2022 12:13 |
| Last Modified: | 27 Sep 2022 12:13 |
| URI: | https://pred.uni-regensburg.de/id/eprint/48073 |
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