Genetic susceptibility to acute graft versus host disease in pediatric patients undergoing HSCT.
Journal
Bone marrow transplantation
ISSN: 1476-5365
Titre abrégé: Bone Marrow Transplant
Pays: England
ID NLM: 8702459
Informations de publication
Date de publication:
11 2021
11 2021
Historique:
received:
08
03
2021
accepted:
21
06
2021
revised:
28
05
2021
pubmed:
4
7
2021
medline:
11
3
2022
entrez:
3
7
2021
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 34215854
doi: 10.1038/s41409-021-01386-8
pii: 10.1038/s41409-021-01386-8
doi:
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
2697-2704Informations de copyright
© 2021. The Author(s), under exclusive licence to Springer Nature Limited.
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