title: Association of IL-1β -511 polymorphism with severe veno-occlusive disease in pediatric-matched allogeneic hematopoietic stem cell transplantation.
abstract: Single nucleotide polymorphisms (SNPs) of the interleukin 1 (IL-1) family have been implicated in acute graft-versus-host disease and mortality postallogeneic hematopoietic stem cell transplantation (HSCT) in adults. Hepatic veno-occlusive disease (VOD) is a well-known complication of HSCT and can result in an increased risk of mortality. In this study, we sought to investigate the association of both patient and donor genotypes at the IL-1β -511 cytidine/thymidine (C/T) polymorphic site with hepatic VOD and mortality in an exclusive pediatric cohort undergoing matched myeloablative allogeneic HSCT. Donor TT genotype was associated with higher cumulative incidence of grade III-IV hepatic VOD at 3 months after transplantation relative to donor CT and CC genotypes (25±13.1% in TT, 2.9±2.9% in CT, and 3.6±3.6% in CC; P=0.024). Neither recipient nor donor IL-1β -511 single nucleotide polymorphisms genotypes were associated with mortality or relapse. Our findings suggest that donor, rather than host, genotype at the IL-1β -511 polymorphic site may associate with higher risk for severe VOD after matched allogeneic HSCT. Our findings challenge the assumption that host factors are exclusively responsible for VOD and suggest a novel role for the donor inflammasome pathway in inducing injury and microvascular disease after HSCT, which merits further study in a larger cohort analysis.
authors.affiliation: Department of Biostatistics, St. Jude Children's Research Hospital, Memphis, TN, USA. lama.elbahlawan@stjude.org
authors.forename: Lama
authors.initials: L
authors.lastname: Elbahlawan
authors.forename: Jennifer
authors.initials: J
authors.lastname: McArthur
authors.forename: Michael W
authors.initials: MW
authors.lastname: Quasney
authors.forename: Deqing
authors.initials: D
authors.lastname: Pei
authors.forename: Kumar
authors.initials: K
authors.lastname: Srivastava
authors.forename: Mary K
authors.initials: MK
authors.lastname: Dahmer
authors.forename: Raymond
authors.initials: R
authors.lastname: Barfield
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D004273:DNA, Neoplasm / Q000235:genetics; D005260:Female; D005838:Genotype; D006086:Graft vs Host Disease / Q000209:etiology* / Q000401:mortality; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects*; D006504:Hepatic Veno-Occlusive Disease / Q000209:etiology* / Q000401:mortality; D006801:Humans; D007223:Infant; D053583:Interleukin-1beta / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011379:Prognosis; D035781:Siblings; D015996:Survival Rate; D014019:Tissue Donors; D014184:Transplantation, Homologous / Q000009:adverse effects*; D055815:Young Adult
chemical_list: D004273:DNA, Neoplasm; D053583:Interleukin-1beta