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Pharmacogenetics of steroid‐responsive acute graft‐versus‐host disease
Author(s) -
Arora Mukta,
Weisdorf Daniel J.,
Shanley Ryan M.,
Thyagarajan Bharat
Publication year - 2017
Publication title -
clinical transplantation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.918
H-Index - 76
eISSN - 1399-0012
pISSN - 0902-0063
DOI - 10.1111/ctr.12949
Subject(s) - medicine , glucocorticoid receptor , snp , glucocorticoid , single nucleotide polymorphism , graft versus host disease , immunology , disease , gene , oncology , bioinformatics , genotype , biology , genetics
Glucocorticoids are central to effective therapy of acute graft‐versus‐host disease ( GVHD ). However, only about half of the patients respond to steroids in initial therapy. Based on postulated mechanisms for anti‐inflammatory effectiveness, we explored genetic variations in glucocorticoid receptor, co‐chaperone proteins, membrane transporters, inflammatory mediators, and variants in the T‐cell receptor complex in hematopoietic cell transplant recipients with acute GVHD requiring treatment with steroids and their donors toward response at day 28 after initiation of therapy. A total of 300 recipient and donor samples were analyzed. Twenty‐three SNP s in 17 genes affecting glucocorticoid pathways were included in the analysis. In multiple regression analysis, donor SNP rs3192177 in the ZAP 70 gene (O.R. 2.8, 95% CI : 1.3‐6.0, P =.008) and donor SNP rs34471628 in the DUSPI gene (O.R. 0.3, 95% CI : 0.1‐1.0, P =.048) were significantly associated with complete or partial response. However, after adjustment for multiple testing, these SNP s did not remain statistically significant. Our results, on this small, exploratory, hypothesis generating analysis suggest that common genetic variation in glucocorticoid pathways may help identify subjects with differential response to glucocorticoids. This needs further assessment in larger datasets and if validated could help identify subjects for alternative treatments and design targeted treatments to overcome steroid resistance.