title: Toll-like receptor polymorphisms in allogeneic hematopoietic cell transplantation.
abstract: To assess the impact of the genetic variation in toll-like receptors (TLRs) on outcome after allogeneic myeloablative conditioning hematopoietic cell transplantation (HCT), we investigated 29 single nucleotide polymorphisms across 10 TLRs in 816 patients and donors. Only donor genotype of TLR8 rs3764879, which is located on the X chromosome, was significantly associated with outcome at the Bonferroni-corrected level P ≤ .001. Male hemizygosity and female homozygosity for the minor allele were significantly associated with disease-free survival (hazard ratio [HR], 1.47 [95% confidence interval {CI}, 1.16 to 1.85]; P = .001). Further analysis stratified by donor sex due to confounding by sex was suggestive for associations with overall survival (male donor: HR, 1.41 [95% CI, 1.09 to 1.83], P = .010; female donor: HR, 2.78 [95% CI, 1.43 to 5.41], P = .003), disease-free survival (male donor: HR, 1.45 [95% CI, 1.12 to 1.87], P = .005; female donor: HR, 2.34 [95% CI, 1.18 to 4.65], P = .015), and treatment-related mortality (male donor: HR, 1.49 [95% CI, 1.09 to 2.04], P = .012; female donor: HR, 3.12 [95% CI, 1.44 to 6.74], P = .004). In conclusion, our findings suggest that the minor allele of TLR8 rs3764879 of the donor is associated with outcome after myeloablative conditioned allogeneic HCT.
authors.affiliation: The Laboratory for Allogeneic Hematopoietic Cell Transplantation, Department of Hematology, Rigshospitalet, Copehnhagen, Denmark. Electronic address: brian@kornblit.dk.
authors.forename: Brian
authors.initials: B
authors.lastname: Kornblit
authors.affiliation: Department of Infectious Diseases and Rheumatology, Institute for Inflammation Research, Rigshospitalet, Copenhagen, Denmark.
authors.forename: Christian
authors.initials: C
authors.lastname: Enevold
authors.affiliation: Division of Biostatistics, Institute for Health and Society, Medical College of Wisconsin, Milwaukee, Wisconsin.
authors.forename: Tao
authors.initials: T
authors.lastname: Wang
authors.affiliation: Center for International Blood and Marrow Transplant Research, Minneapolis, Minnesota.
authors.forename: Stephen
authors.initials: S
authors.lastname: Spellman
authors.affiliation: Center for International Blood and Marrow Transplant Research, Minneapolis, Minnesota.
authors.forename: Mike
authors.initials: M
authors.lastname: Haagenson
authors.affiliation: Clinical Transplant Research, Fred Hutchinson Cancer Research Center, Seattle, Washington.
authors.forename: Stephanie J
authors.initials: SJ
authors.lastname: Lee
authors.affiliation: Department of Infectious Diseases and Rheumatology, Institute for Inflammation Research, Rigshospitalet, Copenhagen, Denmark; Department of Pediatrics and Adolescent Medicine, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.
authors.forename: Klaus
authors.initials: K
authors.lastname: Müller
mesh_terms: D000293:Adolescent; D000328:Adult; D000483:Alleles; D002648:Child; D002675:Child, Preschool; D041321:Chromosomes, Human, X / Q000737:chemistry; D005260:Female; D015870:Gene Expression; D005838:Genotype; D006086:Graft vs Host Disease / Q000517:prevention & control; D019337:Hematologic Neoplasms / Q000276:immunology / Q000401:mortality* / Q000473:pathology / Q000628:therapy; D018380:Hematopoietic Stem Cell Transplantation / Q000401:mortality*; D057898:Hemizygote; D006720:Homozygote; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D008875:Middle Aged; D019653:Myeloablative Agonists / Q000627:therapeutic use; D020641:Polymorphism, Single Nucleotide; D011379:Prognosis; D012737:Sex Factors; D016019:Survival Analysis; D014019:Tissue Donors; D051200:Toll-Like Receptor 8 / Q000235:genetics* / Q000276:immunology; D019172:Transplantation Conditioning; D014184:Transplantation, Homologous; D016896:Treatment Outcome
chemical_list: D007166:Immunosuppressive Agents; D019653:Myeloablative Agonists; C495349:TLR8 protein, human; D051200:Toll-Like Receptor 8
keywords: Allogeneic hematopoietic cell transplantation; Single nucleotide polymorphism; Toll-like receptor 8; Toll-like receptors