Ansari, Marc and Petrykey, Kateryna and Rezgui, Mohamed Aziz and Del Vecchio, Veronica and Cortyl, Jacques and Ameur, Milad and Nava, Tiago and Beaulieu, Patrick and St-Onge, Pascal and Mlakar, Simona Jurkovic and Uppugunduri, Chakradhara Rao S. and Theoret, Yves and Bartelink, Imke H. and Boelens, Jaap-Jan and Bredius, Robbert G. M. and Dalle, Jean-Hugues and Lewis, Victor and Kangarloo, Bill S. and Corbacioglu, Selim and Sinnett, Daniel and Bittencourt, Henrique and Krajinovic, Maja (2021) Genetic susceptibility to acute graft versus host disease in pediatric patients undergoing HSCT. BONE MARROW TRANSPLANTATION, 56 (11). pp. 2697-2704. ISSN 0268-3369, 1476-5365
Full text not available from this repository. (Request a copy)Abstract
The most frequent complication of allogeneic hematopoietic stem cell transplantation is acute Graft versus Host Disease (aGVHD). Proliferation and differentiation of donor T cells initiate inflammatory response affecting the skin, liver, and gastrointestinal tract. Besides recipient-donor HLA disparities, disease type, and the conditioning regimen, variability in the non-HLA genotype have an impact on aGVHD onset, and genetic variability of key cytokines and chemokines was associated with increased risk of aGVHD. To get further insight into the recipient genetic component of aGVHD grades 2-4 in pediatric patients, we performed an exome-wide association study in a discovery cohort (n = 87). Nine loci sustained correction for multiple testing and were analyzed in a validation group (n = 168). Significant associations were replicated for ERC1 rs1046473, PLEK rs3816281, NOP9 rs2332320 and SPRED1 rs11634702 variants through the interaction with non-genetic factors. The ERC1 variant was significant among patients that received the transplant from HLA-matched related individuals (p = 0.03), bone marrow stem cells recipients (p = 0.007), and serotherapy-negative patients (p = 0.004). NOP9, PLEK, and SPRED1 effects were modulated by stem cell source, and serotherapy (p < 0.05). Furthermore, ERC1 and PLEK SNPs correlated with aGVHD 3-4 independently of non-genetic covariates (p = 0.02 and p = 0.003). This study provides additional insight into the genetic component of moderate to severe aGVHD.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | STEM-CELL TRANSPLANTATION; VASCULAR ENDOTHELIUM; BONE-MARROW; MAST-CELLS; HISTOCOMPATIBILITY; GVHD; SPRED1; ASSOCIATION; ACTIVATION; SUPPRESSOR; |
| 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 11:48 |
| Last Modified: | 27 Sep 2022 11:48 |
| URI: | https://pred.uni-regensburg.de/id/eprint/48067 |
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