Genetic associations with immune-mediated outcomes after allogeneic hematopoietic cell transplantation
Blood Advances, ISSN: 2473-9529, Vol: 6, Issue: 8, Page: 2608-2617
2022
- 3Citations
- 10Captures
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Example: if you select the 1-year option for an article published in 2019 and a metric category shows 90%, that means that the article or review is performing better than 90% of the other articles/reviews published in that journal in 2019. If you select the 3-year option for the same article published in 2019 and the metric category shows 90%, that means that the article or review is performing better than 90% of the other articles/reviews published in that journal in 2019, 2018 and 2017.
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Metrics Details
- Citations3
- Citation Indexes3
- Captures10
- Readers10
- 10
Article Description
Previous studies have identified more than 200 genetic variants associated with acute or chronic graft-versus-host disease (aGVHD; cGVHD) or recurrent malignancy after allogeneic hematopoietic cell transplantation (HCT). We tested these candidate donor and recipient variants in a cohort of 4270 HCT recipients of European ancestry and in subcohorts of 1827 sibling and 1447 unrelated recipients who had 10/10 HLA-A, B, C, DRB1, and DQB1-matched donors. We also carried out a genome-wide association study (GWAS) for these same outcomes. The discovery and replication analysis of candidate variants identified a group of closely linked recipient HLA-DPB1 single-nucleotide polymorphisms (SNPs) associated with an increased risk of aGVHD and a corresponding decreased risk of recurrent malignancy after unrelated HCT. These results reflect a correlation with the level of HLA-DPB1 expression previously shown to affect the risks of aGVHD and relapse in unrelated recipients. Our GWAS identified an association of cGVHD with a locus of X-linked recipient intron variants in NHS, a gene that regulates actin remodeling and cell morphology. Evaluation of this association in a second replication cohort did not confirm the original replication results, and we did not reach any definitive conclusion regarding the validity of this discovery. The cohort used for our study is larger than those used in most previous HCT studies but is smaller than those typically used for other genotype-phenotype association studies. Genomic and disease data from our study are available for further analysis in combination with data from other cohorts.
Bibliographic Details
http://www.sciencedirect.com/science/article/pii/S2473952922000192; http://dx.doi.org/10.1182/bloodadvances.2021005620; http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=85129251100&origin=inward; http://www.ncbi.nlm.nih.gov/pubmed/34996099; https://ashpublications.org/bloodadvances/article/6/8/2608/483373/Genetic-associations-with-immune-mediated-outcomes; https://dx.doi.org/10.1182/bloodadvances.2021005620; https://ashpublications.org/bloodadvances/article/doi/10.1182/bloodadvances.2021005620/483373/Genetic-Associations-with-Immune-mediated-Outcomes
American Society of Hematology
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