title: Single Nucleotide Polymorphisms in MORC4, CD14, and TLR4 Are Related to Outcome of Allogeneic Stem Cell Transplantation.
abstract: BACKGROUND
  Non-HLA genes may contribute to the prognosis after hematopoietic stem cell transplantation. We investigated associations between single nucleotide polymorphisms in regions of MORC4, CD14, TLR4, NOD2, SLC22A4, SLC22A5, CARD8, NLRP3, and CLDN2 and the outcomes of patients undergoing allogeneic stem cell transplantation.
  
  
  METHODS
  Single nucleotide polymorphisms in selected regions were determined and analyzed for putative associations with overall mortality and acute graft-versus-host disease. Significant associations were further explored by logistic regression, controlling for additional variables.
  
  
  RESULTS
  A significant association was identified between overall mortality among recipients and a nonsynonymous coding variant of MORC4 (rs6622126) in the recipient genetic makeup (P=0.029). Since MORC4 is located on the X-chromosome, the results were also analyzed separately for males and females. The association between overall mortality for recipients and the risk allele (rs6622126; A) was confirmed for males with respect to genetic makeup of recipients (P=0.012), donor genetic makeup (P=0.004), and the combined allele composition of the donor and recipient (P=0.001). A significant association was also identified between overall mortality and the recipient risk allele of CD14 (rs2569190; P=0.031), TLR4 (rs4986790; P=0.043), and NOD2 (carriage of at least 1 mutant allele of rs2066844, rs2066845, or rs2066847; P=0.048). Among the investigated genes, only the CD14 (rs2569190) recipient risk allele was significantly associated with acute graft-versus-host disease (P=0.023). Logistic regression models confirmed these findings, except for NOD2, and also identified a significant contribution by age at stem cell transplantation (MORC4, CD14, TLR4), diagnosis (CD14, TLR4), and prophylaxis (MORC4).
  
  
  CONCLUSIONS
  Genetic variation in MORC4, CD14, and TLR4 may affect the outcome of allogeneic stem cell transplantation.
authors.affiliation: Department of Medicine, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Norén
authors.affiliation: Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.
authors.forename: Deepti
authors.initials: D
authors.lastname: Verma
authors.affiliation: Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.
authors.forename: Peter
authors.initials: P
authors.lastname: Söderkvist
authors.affiliation: Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.
authors.forename: Tilman
authors.initials: T
authors.lastname: Weisselberg
authors.affiliation: Division of Medical Diagnostics, Region Jönköping County, Jönköping, Sweden.
authors.forename: Jan
authors.initials: J
authors.lastname: Söderman
authors.affiliation: Department of Medical and Health Sciences, Faculty of Health Sciences, Linköping University, Linköping, Sweden.
authors.forename: Kourosh
authors.initials: K
authors.lastname: Lotfi
authors.affiliation: Department of Medicine, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Sven
authors.initials: S
authors.lastname: Almer
mesh_terms: D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D000368:Aged; D002648:Child; D005260:Female; D005819:Genetic Markers; D060005:Genotyping Techniques; D006086:Graft vs Host Disease / Q000235:genetics*; D018380:Hematopoietic Stem Cell Transplantation / Q000401:mortality*; D006801:Humans; D018950:Lipopolysaccharide Receptors / Q000235:genetics*; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D009687:Nuclear Proteins / Q000235:genetics*; D017063:Outcome Assessment, Health Care; D020641:Polymorphism, Single Nucleotide; D012189:Retrospective Studies; D051197:Toll-Like Receptor 4 / Q000235:genetics*; D014184:Transplantation, Homologous; D055815:Young Adult
chemical_list: D005819:Genetic Markers; D018950:Lipopolysaccharide Receptors; C523050:MORC4 protein, human; D009687:Nuclear Proteins; C495345:TLR4 protein, human; D051197:Toll-Like Receptor 4