Faculty Collaboration Database

Toll-like receptor polymorphisms in allogeneic hematopoietic cell transplantation. Biol Blood Marrow Transplant 2015 Feb;21(2):259-65

Date

12/03/2014

Pubmed ID

25464115

Pubmed Central ID

PMC4297590

DOI

10.1016/j.bbmt.2014.09.016

Scopus ID

2-s2.0-84920887412 (requires institutional sign-in at Scopus site)   5 Citations

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.

Author List

Kornblit B, Enevold C, Wang T, Spellman S, Haagenson M, Lee SJ, Müller K

Author

Tao Wang PhD Associate Professor in the Institute for Health and Equity department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Adolescent
Adult
Alleles
Child
Child, Preschool
Chromosomes, Human, X
Female
Gene Expression
Genotype
Graft vs Host Disease
Hematologic Neoplasms
Hematopoietic Stem Cell Transplantation
Hemizygote
Homozygote
Humans
Immunosuppressive Agents
Infant
Infant, Newborn
Male
Middle Aged
Myeloablative Agonists
Polymorphism, Single Nucleotide
Prognosis
Sex Factors
Survival Analysis
Tissue Donors
Toll-Like Receptor 8
Transplantation Conditioning
Transplantation, Homologous
Treatment Outcome