An alpha-defensin gene single nucleotide polymorphism modulates the gut microbiota and may alter the risk of acute graft-versus-host disease

Armin Rashidi; Adam Herman; Antonio L.C. Gomes; Jonathan U. Peled; Robert R. Jenq; Daniel G. Brereton; Christopher Staley; Bruce R. Blazar; Daniel J. Weisdorf

doi:10.1111/bjh.16458

An alpha-defensin gene single nucleotide polymorphism modulates the gut microbiota and may alter the risk of acute graft-versus-host disease

Armin Rashidi, Adam Herman, Antonio L.C. Gomes, Jonathan U. Peled, Robert R. Jenq, Daniel G. Brereton, Christopher Staley, Bruce R. Blazar, Daniel J. Weisdorf

Research output: Contribution to journal › Article › peer-review

4 Scopus citations

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.

Original language	English (US)
Pages (from-to)	926-930
Number of pages	5
Journal	British journal of haematology
Volume	189
Issue number	5
DOIs	https://doi.org/10.1111/bjh.16458
State	Published - Jun 1 2020

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Publisher Copyright:
© 2020 British Society for Haematology and John Wiley & Sons Ltd

Keywords

graft-versus-host disease
microbiota
odoribacter
paneth cell
polymorphism

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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.",

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AU - Rashidi, Armin

AU - Herman, Adam

AU - Gomes, Antonio L.C.

AU - Peled, Jonathan U.

AU - Jenq, Robert R.

AU - Brereton, Daniel G.

AU - Staley, Christopher

AU - Blazar, Bruce R.

AU - Weisdorf, Daniel J.

PY - 2020/6/1

Y1 - 2020/6/1

N2 - 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.

AB - 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.

KW - graft-versus-host disease

KW - microbiota

KW - odoribacter

KW - paneth cell

KW - polymorphism

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An alpha-defensin gene single nucleotide polymorphism modulates the gut microbiota and may alter the risk of acute graft-versus-host disease

Abstract

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Keywords

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