An alpha-defensin gene single nucleotide polymorphism modulates the gut microbiota and may alter the risk of acute graft-versus-host disease.
Armin RashidiAdam HermanAntonio L C GomesJonathan U PeledRobert R JenqDaniel G BreretonChristopher StaleyBruce R BlazarDaniel J WeisdorfPublished in: British journal of haematology (2020)
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.
Keyphrases
- liver failure
- genome wide
- single cell
- cell therapy
- respiratory failure
- stem cell transplantation
- bone marrow
- electronic health record
- stem cells
- hematopoietic stem cell
- gene expression
- big data
- copy number
- dna methylation
- hepatitis b virus
- heavy metals
- high dose
- low dose
- risk assessment
- transcription factor
- data analysis