Genetic polymorphism related to monocyte-macrophage function is associated with graft-versus-host disease

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Hyvarinen , K , Ritari , J , Koskela , S , Niittyvuopio , R , Nihtinen , A , Volin , L , Gallardo , D & Partanen , J 2017 , ' Genetic polymorphism related to monocyte-macrophage function is associated with graft-versus-host disease ' , Scientific Reports , vol. 7 , 15666 . https://doi.org/10.1038/s41598-017-15915-3

Title: Genetic polymorphism related to monocyte-macrophage function is associated with graft-versus-host disease
Author: Hyvarinen, Kati; Ritari, Jarmo; Koskela, Satu; Niittyvuopio, Riitta; Nihtinen, Anne; Volin, Liisa; Gallardo, David; Partanen, Jukka
Contributor: University of Helsinki, Hematologian yksikkö
University of Helsinki, Hematologian yksikkö
University of Helsinki, Clinicum
Date: 2017-11-15
Language: eng
Number of pages: 10
Belongs to series: Scientific Reports
ISSN: 2045-2322
URI: http://hdl.handle.net/10138/229012
Abstract: Despite detailed human leukocyte antigen (HLA) matching and modern immunosuppressive therapy, severe graft-versus-host disease (GvHD) remains a major hurdle for successful allogeneic hematopoietic stem cell transplantation (HSCT). As the genetic diversity in GvHD complicates the systematic discovery of associated variants across populations, we studied 122 GvHD-associated single nucleotide polymorphisms (SNPs) in 492 HLA-matched sibling HSCT donor-recipient pairs from Finland and Spain. The association between these candidate SNPs and grade III-IV acute GvHD and extensive chronic GvHD was assessed. The functional effects of the variants were determined using expression and cytokine quantitative trait loci (QTL) database analyses. Clear heterogeneity was observed in the associated markers between the two populations. Interestingly, the majority of markers, such as those annotated to IL1, IL23R, TLR9, TNF, and NOD2 genes, are related to the immunological response by monocytes-macrophages to microbes, a step that precedes GvHD as a result of intestinal lesions. Furthermore, cytokine QTL analysis showed that the GvHD-associated markers regulate IL1 beta, IFN gamma, and IL6 responses. These results support a crucial role for the anti-microbial response in GvHD risk. Furthermore, despite apparent heterogeneity in the genetic markers associated with GvHD, it was possible to identify a biological pathway shared by most markers in both populations.
Subject: STEM-CELL TRANSPLANTATION
SINGLE NUCLEOTIDE POLYMORPHISMS
AML PATIENTS
ACUTE GVHD
RISK
SUSCEPTIBILITY
BLOOD
PLINK
3122 Cancers
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