Impact of cytokine gene polymorphisms on risk and treatment outcomes of aplastic anemia

Ann Hematol. 2011 May;90(5):515-21. doi: 10.1007/s00277-010-1102-2. Epub 2010 Oct 16.


Autoreactive cytotoxic T cells play a key role in the pathogenesis of aplastic anemia (AA) by myelosuppressive cytokines including interferon-gamma, tumor necrosis factor alpha, and transforming growth factor beta. The purpose of this study is to determine which single nucleotide polymorphisms (SNPs) in cytokine genes were relevant to AA risk and whether the relevant SNPs were associated with response to immunosuppressive therapy (IST). Among 84 screened patients, 80 patients confirmed as having acquired AA, and 84 age- and sex-matched healthy controls were analyzed consecutively. We genotyped ten polymorphisms in three cytokine genes (IFNG, TNF, and TGFB1) and FAS gene. We assessed the association between polymorphisms and AA risk, and the association between polymorphisms and response to IST in three genetic models (dominant, recessive, and additive). The IFNG -2,353 T allele (dominant model, OR = 0.43, p = .012) and TCA haplotype (dominant model, OR = 0.50, p = .038) were significantly associated with the development of AA. In addition, this relevant IFNG -2,353 T allele and TCA haplotype were related to the response of IST (dominant model, OR = 0.076, p = .034). Concerning TGFB1, although its polymorphisms are not related to AA susceptibility, P10L T allele (recessive model, OR = 0.18, p = .038) and CT haplotype (dominant model, OR = 5.68, p = .038) were associated with response to IST. This exploratory study concurred with prior studies indicating that polymorphisms in IFNG are related to AA susceptibility. In addition, it was found that polymorphisms in IFNG and TGFB1 are associated with response to IST.

Publication types

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

MeSH terms

  • Adult
  • Alleles
  • Anemia, Aplastic / drug therapy*
  • Anemia, Aplastic / genetics*
  • Antilymphocyte Serum / therapeutic use
  • Cyclosporine / therapeutic use
  • Female
  • Genes, Dominant
  • Genetic Association Studies
  • Genetic Predisposition to Disease
  • Haplotypes
  • Humans
  • Immunosuppressive Agents / therapeutic use*
  • Interferon-gamma / genetics*
  • Male
  • Middle Aged
  • Models, Genetic
  • Polymorphism, Single Nucleotide*
  • Republic of Korea
  • Risk Factors
  • Transforming Growth Factor beta1 / genetics*


  • Antilymphocyte Serum
  • Immunosuppressive Agents
  • TGFB1 protein, human
  • Transforming Growth Factor beta1
  • Interferon-gamma
  • Cyclosporine