PMID- 29142307
OWN - NLM
STAT- MEDLINE
DCOM- 20190703
LR  - 20190703
IS  - 2045-2322 (Electronic)
IS  - 2045-2322 (Linking)
VI  - 7
IP  - 1
DP  - 2017 Nov 15
TI  - Genetic polymorphism related to monocyte-macrophage function is associated with 
      graft-versus-host disease.
PG  - 15666
LID - 10.1038/s41598-017-15915-3 [doi]
LID - 15666
AB  - 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 IL1beta, IFNgamma, 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.
FAU - Hyvarinen, Kati
AU  - Hyvarinen K
AUID- ORCID: 0000-0003-4605-2837
AD  - Finnish Red Cross Blood Service, Helsinki, Finland. 
      kati.hyvarinen@bloodservice.fi.
FAU - Ritari, Jarmo
AU  - Ritari J
AD  - Finnish Red Cross Blood Service, Helsinki, Finland.
FAU - Koskela, Satu
AU  - Koskela S
AD  - Finnish Red Cross Blood Service, Helsinki, Finland.
FAU - Niittyvuopio, Riitta
AU  - Niittyvuopio R
AD  - Helsinki University Hospital, Comprehensive Cancer Center, Stem Cell 
      Transplantation Unit, Helsinki, Finland.
FAU - Nihtinen, Anne
AU  - Nihtinen A
AD  - Helsinki University Hospital, Comprehensive Cancer Center, Stem Cell 
      Transplantation Unit, Helsinki, Finland.
FAU - Volin, Liisa
AU  - Volin L
AD  - Helsinki University Hospital, Comprehensive Cancer Center, Stem Cell 
      Transplantation Unit, Helsinki, Finland.
FAU - Gallardo, David
AU  - Gallardo D
AD  - Department of Hematology, Institut Catala d'Oncologia, Hospital Dr. Josep Trueta, 
      Girona, Spain.
FAU - Partanen, Jukka
AU  - Partanen J
AUID- ORCID: 0000-0001-6681-4734
AD  - Finnish Red Cross Blood Service, Helsinki, Finland.
LA  - eng
PT  - Journal Article
DEP - 20171115
PL  - England
TA  - Sci Rep
JT  - Scientific reports
JID - 101563288
RN  - 0 (Cytokines)
RN  - 0 (HLA Antigens)
RN  - 0 (IL23R protein, human)
RN  - 0 (NOD2 protein, human)
RN  - 0 (Nod2 Signaling Adaptor Protein)
RN  - 0 (Receptors, Interleukin)
RN  - 0 (Toll-Like Receptor 9)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Cytokines/genetics
MH  - Female
MH  - Finland
MH  - *Genetic Association Studies
MH  - Graft vs Host Disease/*genetics/pathology
MH  - HLA Antigens/genetics
MH  - *Hematopoietic Stem Cell Transplantation
MH  - Humans
MH  - Macrophages/metabolism/pathology
MH  - Male
MH  - Middle Aged
MH  - Nod2 Signaling Adaptor Protein/genetics
MH  - Polymorphism, Single Nucleotide
MH  - Quantitative Trait Loci/*genetics
MH  - Receptors, Interleukin
MH  - Siblings
MH  - Toll-Like Receptor 9/genetics
MH  - Transplantation, Homologous/adverse effects
PMC - PMC5688060
COIS- The authors declare that they have no competing interests.
EDAT- 2017/11/17 06:00
MHDA- 2019/07/04 06:00
PMCR- 2017/11/15
CRDT- 2017/11/17 06:00
PHST- 2017/06/09 00:00 [received]
PHST- 2017/11/03 00:00 [accepted]
PHST- 2017/11/17 06:00 [entrez]
PHST- 2017/11/17 06:00 [pubmed]
PHST- 2019/07/04 06:00 [medline]
PHST- 2017/11/15 00:00 [pmc-release]
AID - 10.1038/s41598-017-15915-3 [pii]
AID - 15915 [pii]
AID - 10.1038/s41598-017-15915-3 [doi]
PST - epublish
SO  - Sci Rep. 2017 Nov 15;7(1):15666. doi: 10.1038/s41598-017-15915-3.