IL28B gene polymorphisms and Th1/Th2 cytokine levels might be associated with HTLV-associated arthropathy

Cytokine. 2016 Jan:77:79-87. doi: 10.1016/j.cyto.2015.11.004. Epub 2015 Nov 5.

Abstract

The present study is the first investigation of the association between single nucleotide polymorphisms (SNPs - rs8099917, rs12979860 and rs8103142) of the IL28B gene and the development of human T-lymphotropic virus (HTLV)-associated arthropathy (HAA). Individuals with HAA exhibited low interleukin (IL) 6 (p<0.05) and high IL-10 (p<0.05) levels compared with asymptomatic patients. TNF-α/CD4(+) T cell count, TNF-α/CD8(+) T cell count and IFN-γ/proviral load positively correlated in asymptomatic patients. The allelic and genotypic frequencies did not differ between patients with HAA and asymptomatic patients. Seven haplotypes were detected in the investigated population, with haplotype CCT (p<0.05) being the most frequent among the HTLV-infected individuals, while haplotype TTG (p<0.05) was detected in the group with HAA only. Compared with asymptomatic patients, individuals with HAA and genotype TT (rs8099917) exhibited larger numbers of CD8(+) T cells (p<0.05) and higher proviral load levels (p<0.05). Those patients with HAA and genotypes CC (rs12979860) and TT (rs8103142) exhibited high TNF-β (p<0.05) and IFN-γ (p<0.05) levels. Those patients with HAA and genotype CT/TT (rs12979860) exhibited high IL-10 levels (p<0.05). These results suggest that haplotypes CCT and TTG might be associated with susceptibility to HTLV infection and progression to HAA, respectively. Genotype TT (rs8099917) might be a risk factor for elevation of the proviral load and CD8(+) T cell count. In addition, genotypes CC (rs12979860) and TT (rs8103142) seem to be associated with increased TNF-β and IFN-γ levels.

Keywords: HTLV-associated arthropathy; IL-28B; rs12979860; rs8099917; rs8103142.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alleles
  • Arthritis, Infectious / genetics
  • Arthritis, Infectious / metabolism
  • Arthritis, Infectious / virology*
  • CD4-Positive T-Lymphocytes / metabolism
  • CD8-Positive T-Lymphocytes / metabolism
  • Cytokines / metabolism*
  • Deltaretrovirus / physiology*
  • Deltaretrovirus Infections / genetics
  • Deltaretrovirus Infections / metabolism
  • Deltaretrovirus Infections / virology*
  • Female
  • Gene Frequency
  • Genotype
  • Haplotypes
  • Host-Pathogen Interactions
  • Humans
  • Interferon-gamma / metabolism
  • Interferons
  • Interleukin-10 / metabolism
  • Interleukin-6 / metabolism
  • Interleukins / genetics*
  • Lymphocyte Count
  • Male
  • Polymorphism, Single Nucleotide*
  • Th1 Cells / metabolism
  • Th2 Cells / metabolism
  • Tumor Necrosis Factor-alpha / metabolism
  • Viral Load

Substances

  • Cytokines
  • interferon-lambda, human
  • Interleukin-6
  • Interleukins
  • Tumor Necrosis Factor-alpha
  • Interleukin-10
  • Interferon-gamma
  • Interferons