RANTES polymorphisms and the risk of graft-versus-host disease in human leukocyte antigen-matched sibling allogeneic hematopoietic stem cell transplantation

Acta Haematol. 2013;129(3):137-45. doi: 10.1159/000343273. Epub 2012 Nov 30.

Abstract

We investigated the association between RANTES (regulated upon activation, normal T cell expressed and secreted) polymorphisms and clinical outcomes in patients treated with allogeneic hematopoietic stem cell transplantation (allo-HSCT). Three RANTES gene polymorphisms, i.e., -403G/A (rs2107538), -28C/G (rs2280788) and In1.1T/C (rs2280789), were genotyped, and the effects of the genotypes and haplotypes of RANTES on clinical outcomes were analyzed. The competing risk regression analysis was used to investigate the relationship between the polymorphisms and the cumulative risk of graft-versus-host disease (GVHD). An AGC haplotype in a recessive model showed significant harmful effects on the cumulative risk of acute GVHD and relapse-free survival (adjusted hazard ratios 2.42 and 2.71, 95% confidence intervals 1.29-4.55 and 1.30-5.64; p = 0.018 and 0.024, respectively), whereas a GCT haplotype did not. RANTES polymorphisms were not significantly associated with overall survival and the risk of chronic GVHD. This study suggests that RANTES polymorphisms might be associated with the occurrence of acute GVHD rather than of chronic GVHD and also of relapse-free survival in the patients treated with allo-HSCT. Further larger prospective investigations are needed to establish the role of RANTES polymorphisms in patients treated with allo-HSCT.

Publication types

  • Clinical Trial
  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Disease
  • Adolescent
  • Adult
  • Chemokine CCL5 / genetics*
  • Chronic Disease
  • Disease-Free Survival
  • Female
  • Graft vs Host Disease* / etiology
  • Graft vs Host Disease* / genetics
  • Graft vs Host Disease* / mortality
  • Graft vs Host Disease* / therapy
  • HLA Antigens
  • Haplotypes
  • Hematologic Neoplasms* / genetics
  • Hematologic Neoplasms* / mortality
  • Hematologic Neoplasms* / therapy
  • Hematopoietic Stem Cell Transplantation*
  • Humans
  • Male
  • Middle Aged
  • Polymorphism, Genetic*
  • Risk Factors
  • Siblings
  • Survival Rate
  • Transplantation, Homologous

Substances

  • CCL5 protein, human
  • Chemokine CCL5
  • HLA Antigens