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Single Nucleotide Polymorphisms in MORC4, CD14, and TLR4 Are Related to Outcome of Allogeneic Stem Cell Transplantation
Karolinska Institute, Sweden; Regional Jonköping County, Sweden.
Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Health Sciences.
Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Pathology and Clinical Genetics.
Linköping University, Department of Clinical and Experimental Medicine, Division of Inflammation Medicine. Linköping University, Faculty of Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Gastroentorology.
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2016 (English)In: Annals of Transplantation, ISSN 1425-9524, E-ISSN 2329-0358, Vol. 21, 56-67 p.Article in journal (Refereed) PublishedText
Abstract [en]

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. Material/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.

Place, publisher, year, edition, pages
Warsaw, Poland: International Scientific Literature , 2016. Vol. 21, 56-67 p.
Keyword [en]
Association Studies; Genetic Predisposition to Disease; Graft vs. Host Disease; Polymorphism, Single Nucleotide; Transplantation, Homologous
National Category
Clinical Medicine
Identifiers
URN: urn:nbn:se:liu:diva-126266ISI: 000371110000001OAI: oai:DiVA.org:liu-126266DiVA: diva2:913413
Available from: 2016-03-21 Created: 2016-03-21 Last updated: 2016-04-07Bibliographically approved

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Verma, DeeptiSöderkvist, PeterWeisselberg, TilmanLotfi, Kourosh
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Division of Microbiology and Molecular MedicineFaculty of Health SciencesDivision of Cell BiologyDepartment of Clinical Pathology and Clinical GeneticsDivision of Inflammation MedicineDepartment of GastroentorologyDivision of Drug ResearchFaculty of Medicine and Health SciencesDepartment of Clinical Pharmacology
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Annals of Transplantation
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