Protective role of interleukin-10 promoter gene polymorphism in the pathogenesis of invasive pulmonary aspergillosis after allogeneic stem cell transplantation

Bone Marrow Transplant. 2005 Dec;36(12):1089-95. doi: 10.1038/sj.bmt.1705181.

Abstract

The current study attempted to evaluate the association between the IL-10 promoter gene single nucleotide polymorphism (SNP) and invasive pulmonary aspergillosis (IPA) after allogeneic stem cell transplantation (SCT) in 105 patients. Three single-nucleotide polymorphisms were investigated in the proximal region of the IL-10 promoter gene (-1082/-819/-592). Two haplotypes (1082*A/819*T/592*A [ATA] and 1082*A/819*C/592*C [ACC]) were found in the current study. The overall incidence of IPA was estimated as 14.1+/-4.5% with a median onset at 186 days post-transplant (62 approximately 405 days). An increased occurrence of IPA was noted dependent on the IL-10 haplotype (0% vs 11.5+/-6.4% vs 19.7+/-7.7% for ACC/ACC vs ATA/ACC vs ATA/ATA haplotype, P=0.0307 when comparing ACC with non-ACC haplotype). In a multivariate survival analysis using Cox's proportional hazard model, the IL-10 promoter gene SNPs were identified as an independent predictive factor for the development of IPA (P=0.012, hazard ratio (HR) 9.3), along with an histocompatibility leukocyte antigen (HLA)-identical donor (P=0.005, HR 16.3), the CD34+ cell dose transplanted (P=0.004, HR 26.5), and time-dependent chronic graft-versus-host disease (GVHD; P=0.049, HR 16.0). The IL-10 ACC haplotype was found to have an apparent protective role in the development of IPA after allogeneic transplantation, regardless of HLA-disparity or chronic GVHD.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Antigens, CD34 / biosynthesis
  • Aspergillosis / microbiology*
  • Aspergillosis / therapy*
  • Female
  • Graft vs Host Disease / therapy
  • HLA Antigens / chemistry
  • Haplotypes
  • Humans
  • Interleukin-10 / genetics*
  • Lung / microbiology*
  • Lung / pathology
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Polymorphism, Genetic*
  • Polymorphism, Single Nucleotide
  • Promoter Regions, Genetic*
  • Proportional Hazards Models
  • Stem Cell Transplantation / adverse effects*
  • Time Factors
  • Transplantation, Homologous / adverse effects*
  • Treatment Outcome

Substances

  • Antigens, CD34
  • HLA Antigens
  • Interleukin-10