Genetic variation of TNF-α and IL-10, IL-12, IL-17 genes and association with torque teno virus infection post hematopoietic stem cell transplantation.

Abstract

Little is known about the role of genetic variation in the genes for cytokines and susceptibility to viral infection especially torque teno virus (TTV) following allogeneic hematopoietic stem cell transplantation. In this study, the association between interleukin-12, interleukin-17, interleukin-10 (IL-12,-17,-10) and tumor necrosis factor-α (TNF-α) polymorphisms was evaluated in patients with TTV infection who underwent allogeneic hematopoietic stem cell transplantation from South of Iran. The single nucleotide polymorphisms in the cytokine genes including IL-12 (-1188A/C), IL-17 (-197G/A), IL-10 (-1082G/A, -819C/T and -592C/A) and TNF-α (-308 G/A) were analyzed by PCR-RFLP methods. While our results did not show any association between IL-17, IL-12 and IL-10 (-819C/T and -1082G/A) polymorphisms and TTV infection status, heterozygote genotype of IL-10 (-592C/A) had direct correlation with TTV infection and A allele of TNF-α (-308G/A) showed a protective effect against TTV infection (P=0.05 and P=0.025, respectively). Within the group of patients who experienced acute graft-versus-host disease, the AA genotype and the A allele of IL-17 (-197 G/A) were significantly higher in non-infected patients compared to infected ones (P=0.024 and P=0.057, respectively). It was also observed that among infected patients, the GG genotype of IL-17 and AA genotype of TNF-α were significantly increased in hematopoietic stem cell transplanted patients with low grade (grade I+II) acute graft-versus-host disease compared to high grade (grade III and IV) disease (P=0.056 and P=0.056, respectively). Taken together, genetic variation of IL-10 (-592C/A) and TNF-α (-308G/A) genes might be associated with susceptibility to TTV infection post hematopoietic stem cell transplantation. Keywords: TNF-α; interleukins; torque teno virus (TTV); hematopoietic stem cell transplantation (HSCT); graft versus host disease (GvHD).