An alpha-defensin gene single nucleotide polymorphism modulates the gut microbiota and may alter the risk of acute graft-versus-host disease Journal Article
| Authors: | Rashidi, A.; Herman, A.; Gomes, A. L. C.; Peled, J. U.; Jenq, R. R.; Brereton, D. G.; Staley, C.; Blazar, B. R.; Weisdorf, D. J. |
| Article Title: | An alpha-defensin gene single nucleotide polymorphism modulates the gut microbiota and may alter the risk of acute graft-versus-host disease |
| Abstract: | We previously reported a protective association between single nucleotide polymorphisms (SNPs; rs4415345G and rs4610776A alleles) of Paneth cell α-defensin-5 against acute graft-versus-host disease (aGVHD). Because dysbiosis has been associated with aGVHD, we hypothesized that these SNPs may have a gut microbiota signature. In Lasso regression analysis of 248 healthy individuals, rs4415345G was associated with a higher abundance of Odoribacter splanchnicus, an anaerobic butyrogenic commensal. In multivariable analysis of data from 613 allogeneic haematopoietic cell transplant recipients, peri-engraftment presence of O. splanchnicus was associated with ~50% lower risk for grade II–IV aGVHD (hazard ratio 0·53, 95% confidence interval 0·28–1·00, P = 0·05). O. splanchnicus may protect rs4415345G individuals against aGVHD. © 2020 British Society for Haematology and John Wiley & Sons Ltd |
| Keywords: | adult; controlled study; treatment outcome; gene sequence; major clinical study; single nucleotide polymorphism; united states; allele; demography; gene amplification; gene expression; gene locus; genetic association; gene frequency; prediction; risk factor; acute graft versus host disease; disease severity; allogeneic hematopoietic stem cell transplantation; colitis; cytokine production; intestine flora; risk reduction; rna 16s; volunteer; butyric acid; tryptophan; polymorphism; paneth cell; graft-versus-host disease; microbiota; bacteroidetes; taxonomy; inflammatory bowel disease; alpha defensin; metagenomics; human; priority journal; article; anaerobic bacterium; population abundance; odoribacter; alpha defensin gene; odoribacter splanchnicus |
| Journal Title: | British Journal of Haematology |
| Volume: | 189 |
| Issue: | 5 |
| ISSN: | 0007-1048 |
| Publisher: | John Wiley & Sons |
| Date Published: | 2020-06-01 |
| Start Page: | 926 |
| End Page: | 930 |
| Language: | English |
| DOI: | 10.1111/bjh.16458 |
| PUBMED: | 32086815 |
| PROVIDER: | scopus |
| PMCID: | PMC7536617 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 1 July 2020 -- Source: Scopus |
Altmetric
Citation Impact
BMJ Impact Analytics
Related MSK Work