title: Risk stratification of organ-specific GVHD can be improved by single-nucleotide polymorphism-based risk models.
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.
authors.affiliation: Allogeneic blood and marrow transplantation program, Department of Medical Oncology and Hematology, Princess Margaret Hospital, Toronto, ON, Canada.
authors.forename: D
authors.initials: D
authors.lastname: Kim
authors.affiliation: Bioinformatics, Samsung Biomedical Research Institute, Seoul, South Korea.
authors.forename: H-H
authors.initials: HH
authors.lastname: Won
authors.affiliation: Department of Biostatistics, Princess Margaret Hospital, Toronto, ON, Canada.
authors.forename: S
authors.initials: S
authors.lastname: Su
authors.affiliation: Department of Biostatistics, Princess Margaret Hospital, Toronto, ON, Canada.
authors.forename: L
authors.initials: L
authors.lastname: Cheng
authors.affiliation: Department of Biostatistics, Princess Margaret Hospital, Toronto, ON, Canada.
authors.forename: W
authors.initials: W
authors.lastname: Xu
authors.affiliation: Allogeneic blood and marrow transplantation program, Department of Medical Oncology and Hematology, Princess Margaret Hospital, Toronto, ON, Canada.
authors.forename: N
authors.initials: N
authors.lastname: Hamad
authors.affiliation: Allogeneic blood and marrow transplantation program, Department of Medical Oncology and Hematology, Princess Margaret Hospital, Toronto, ON, Canada.
authors.forename: J
authors.initials: J
authors.lastname: Uhm
authors.affiliation: Allogeneic blood and marrow transplantation program, Department of Medical Oncology and Hematology, Princess Margaret Hospital, Toronto, ON, Canada.
authors.forename: V
authors.initials: V
authors.lastname: Gupta
authors.affiliation: Allogeneic blood and marrow transplantation program, Department of Medical Oncology and Hematology, Princess Margaret Hospital, Toronto, ON, Canada.
authors.forename: J
authors.initials: J
authors.lastname: Kuruvilla
authors.affiliation: Allogeneic blood and marrow transplantation program, Department of Medical Oncology and Hematology, Princess Margaret Hospital, Toronto, ON, Canada.
authors.forename: H A
authors.initials: HA
authors.lastname: Messner
authors.affiliation: Allogeneic blood and marrow transplantation program, Department of Medical Oncology and Hematology, Princess Margaret Hospital, Toronto, ON, Canada.
authors.forename: J H
authors.initials: JH
authors.lastname: Lipton
mesh_terms: D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D000368:Aged; D002908:Chronic Disease; D005260:Female; D005819:Genetic Markers / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000453:epidemiology / Q000235:genetics; D005838:Genotype; D006086:Graft vs Host Disease / Q000453:epidemiology* / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D008957:Models, Genetic; D015999:Multivariate Analysis; D010982:Platelet-Derived Growth Factor / Q000378:metabolism; D020641:Polymorphism, Single Nucleotide; D017452:Receptors, IgG / Q000235:genetics*; D012307:Risk Factors; D016212:Transforming Growth Factor beta / Q000378:metabolism; D053773:Transforming Growth Factor beta1 / Q000235:genetics*; D055815:Young Adult; D019014:fas Receptor / Q000235:genetics*
chemical_list: C491901:FAS protein, human; C445323:FCGR2A protein, human; D005819:Genetic Markers; D010982:Platelet-Derived Growth Factor; D017452:Receptors, IgG; C508960:TGFB1 protein, human; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D019014:fas Receptor