Risk stratification of organ-specific GVHD can be improved by single-nucleotide polymorphism-based risk models

D. Kim, H. H. Won, S. Su, L. Cheng, W. Xu, N. Hamad, Jieun Uhm, V. Gupta, J. Kuruvilla, H. A. Messner, J. H. Lipton

Research output: Contribution to journalArticle

11 Scopus citations

Abstract

We aimed to develop a risk model, based on single-nucleotide polymorphism (SNP) markers associated with an increased risk of organ-specific GVHD in 394 transplant pairs. A total of 259 SNPs were genotyped in 53 genes and evaluated for their associated risk of organ-specific GVHD. Risk models were generated using both clinical factors and genetic SNP markers. Patients were stratified by quartiles according to their risk scores and then categorized into three groups (low, intermediate and high risk) according to this model. We compared the risk of overall and organ-specific GVHD amongst these groups. Several SNP markers in the cytokine-, apoptosis-, TGF-β- and PDGF-mediated pathways were identified as correlative markers of acute and chronic GVHD. Each organ-specific GVHD shared some common biologic pathway such as cytokine, TGF-β- or PDGF-mediated pathways. However, we also identified different SNP markers that correlated with increased risk of organ-specific GVHD (for example, FCGR2A SNP for oral GVHD, and FAS and TGFB1 SNP for lung GVHD). The incorporation of genetic risk factors into the clinical factors risk model improved stratification power for organ-specific GVHD. The SNP-based approach was suggested to improve risk stratification of organ-specific GVHD.

Original languageEnglish
Pages (from-to)649-656
Number of pages8
JournalBone Marrow Transplantation
Volume49
Issue number5
DOIs
StatePublished - 2014 Jan 1

Keywords

  • GVHD
  • Single-nucleotide polymorphism
  • risk model

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    Kim, D., Won, H. H., Su, S., Cheng, L., Xu, W., Hamad, N., Uhm, J., Gupta, V., Kuruvilla, J., Messner, H. A., & Lipton, J. H. (2014). Risk stratification of organ-specific GVHD can be improved by single-nucleotide polymorphism-based risk models. Bone Marrow Transplantation, 49(5), 649-656. https://doi.org/10.1038/bmt.2014.20