HSP70-hom gene polymorphism in allogeneic hematopoietic stem-cell transplant recipients correlates with the development of acute graft-versus-host disease

Transplantation. 2005 Apr 15;79(7):815-20. doi: 10.1097/01.tp.0000153157.97736.2c.

Abstract

Background: A number of genetic polymorphisms have been shown to be associated with the outcome after allogeneic hematopoietic stem-cell transplantation (HSCT). In the present study, HSP70-hom polymorphism (+2763 G/A) was analyzed in the patients and donors of allogeneic HSCT in relation to transplantation outcome, susceptibility for generation of severe toxic lesions, and acute (a) graft-versus-host disease (GVHD).

Methods: One hundred thirty-three recipients of allogeneic hematopoietic stem cells and 64 haploidentical and matched unrelated donors were investigated. All these individuals were typed for dimorphism within the HSP70-hom gene (+2763 G/A) with the use of amplification refractory mutation system technique. RESULTS.: Patients with the HSP-AA homozygous genotype presented more frequently with grade II to IV toxic lesions (12 of 14 vs. 61 of 105, P = 0.039) and aGVHD (12 of 16 vs. 56 of 114, P = 0.045). Conversely, DRB1*11 was associated with a lower risk of aGVHD manifestation (10 of 31 vs. 58 of 99, P = 0.009). These contrary associations of HSP-AA and DRB1*11 with the risk of aGVHD were confirmed using logistic regression modeling in multivariable analysis (HSP-AA, odds ratio [OR] = 3.833, P = 0.004; DRB1*11, OR = 0.224, P = 0.048). None of donor HSP genotypes or patient-donor incompatibility within HSP alleles was associated with susceptibility to toxic complications or aGVHD.

Conclusions: Polymorphism of the HSP70-hom gene is associated with the development of posttransplant complications. Recipient HSP-AA homozygous genotype is a risk factor for aGVHD.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Disease
  • Adolescent
  • Adult
  • Child
  • Child, Preschool
  • Donor Selection
  • Female
  • Genotype
  • Graft vs Host Disease / genetics*
  • Graft vs Host Disease / immunology*
  • HLA-DR Antigens / immunology
  • HLA-DRB1 Chains
  • HSP70 Heat-Shock Proteins / genetics*
  • Hematopoietic Stem Cell Transplantation*
  • Homozygote
  • Humans
  • Infant
  • Male
  • Middle Aged
  • Polymorphism, Genetic / genetics*
  • Risk Factors
  • Transplantation
  • Transplantation Conditioning
  • Transplantation, Homologous
  • Treatment Outcome

Substances

  • HLA-DR Antigens
  • HLA-DRB1 Chains
  • HSP70 Heat-Shock Proteins