title: Cytokine gene polymorphisms and graft-versus-host disease in children after matched sibling hematopoietic stem cell transplantation: a single-center experience.
abstract: Various polymorphisms in cytokine genes have recently been investigated as candidate risk factors in allogeneic hematopoetic stem cell transplantation (allo-HSCT). We retrospectively analyzed specific polymorphisms in genes for interleukin (IL)-10, IL-6, tumor-necrosis factor alpha (TNF-α) and interferon gamma (IFN-γ) in a pediatric cohort of 57 histocompatibility leucocyte antigen (HLA)-identical sibling myeloablative transplants. Both recipient and donor genotypes were tested for association with graft-versus-host disease (GVHD) by statistical methods including Cox regression analysis. We found a significant association between the IL-10 promoter haplotype polymorphisms at positions -1082, -819 and -592 with the occurrence of severe (grades III-IV) acute GVHD (aGVHD). Recipients with the haplotype GCC had a statistically significant decreased risk of severe aGVHD (hazard risk (HR)=0.20, 95% confidence interval (CI): 0.06-0.67) in comparison with patients with other IL-10 haplotypes (P=0.008). Transplant-related mortality at 1 year was significantly lower in recipients with this haplotype (HR=0.17, 95% CI: 0.012-0.320) versus other IL-10 haplotypes (P=0.03), whereas overall survival was not influenced by IL-10 haplotype polymorphisms. In multivariate analysis, the presence of the IL-10 GCC haplotype was found as the only variable associated with a statistically significant decreased hazard of severe aGVHD development (P=0.02, HR=0.21, 95% CI: 0.05-0.78). These results suggest that pediatric patients possessing the IL-10 GCC haplotype may be protected from the occurrence of severe aGVHD in the setting of matched sibling HSCT.
authors.affiliation: Stem Cell Transplant Unit, Aghia Sophia Children's Hospital, Thivon and Papadiamantopoulou, Athens, Greece. evgoussetis@gmail.com
authors.forename: Evgenios
authors.initials: E
authors.lastname: Goussetis
authors.forename: Ioanna
authors.initials: I
authors.lastname: Varela
authors.forename: Ioulia
authors.initials: I
authors.lastname: Peristeri
authors.forename: Vasiliki
authors.initials: V
authors.lastname: Kitra
authors.forename: Kleopatra
authors.initials: K
authors.lastname: Spanou
authors.forename: Olga
authors.initials: O
authors.lastname: Moraloglou
authors.forename: Anna
authors.initials: A
authors.lastname: Paisiou
authors.forename: Sofia
authors.initials: S
authors.lastname: Karatasaki
authors.forename: Alexandra
authors.initials: A
authors.lastname: Soldatou
authors.forename: Nikki
authors.initials: N
authors.lastname: Constantinidou
authors.forename: Stelios
authors.initials: S
authors.lastname: Graphakos
mesh_terms: D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D016207:Cytokines / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D020022:Genetic Predisposition to Disease; D006086:Graft vs Host Disease / Q000235:genetics* / Q000276:immunology* / Q000401:mortality; D006115:Greece; D006239:Haplotypes; D018380:Hematopoietic Stem Cell Transplantation; D006648:Histocompatibility; D006650:Histocompatibility Testing; D006801:Humans; D007223:Infant; D011110:Polymorphism, Genetic; D012189:Retrospective Studies; D035781:Siblings; D016019:Survival Analysis; D019172:Transplantation Conditioning
chemical_list: D016207:Cytokines