Replication of associations between genetic polymorphisms and chronic graft-versus-host disease.

Publication Type:

Journal Article

Source:

Blood, Volume 128, Issue 20, p.2450-2456 (2016)

Abstract:

Previous studies have identified single-nucleotide polymorphisms (SNPs) associated with the risk of chronic graft-versus-host disease (GVHD) after allogeneic hematopoietic cell transplantation (HCT). The current study determined whether these associations could be replicated in large cohorts of donors and recipients. Each SNP was tested with cohorts of patients having the same donor type (HLA-matched related, unrelated or both) reported in the original publication, and testing was limited to the same genome (recipient or donor) and genetic model (dominant, recessive or allelic) reported in the original study. The 21 SNPs reported in this study represent 19 genes, and the analysis encompassed 22 SNP association tests. The hazard ratio point estimates and risk ratio point estimates corresponding to odds ratios in previous studies consistently fall outside the 95% confidence intervals of hazard ratio estimates in the current study. Despite the large size of the cohorts available for the current study, the 95% confidence intervals for most hazard ratios did not exclude 1.0. Three SNPs representing CTLA4, HPSE and IL1R1 showed evidence of association with the risk of chronic GVHD in unrelated donor-recipient pairs from one cohort, but none of these associations was replicated when tested in unrelated donor-recipient pairs from an independent cohort. Two SNPs representing CCR6 and FGFR1OP showed possible associations with the risk of chronic GVHD in related donor-recipient pairs but not in unrelated donor-recipient pairs. These results remain to be tested for replication in other cohorts of related donor-recipient pairs.