Toll-like receptor gene polymorphisms in patients with myeloproliferative neoplasms

Mol Biol Rep. 2021 Jun;48(6):4995-5001. doi: 10.1007/s11033-021-06238-8. Epub 2021 Jun 30.


Toll-like receptors (TLRs) are a family of transmembrane receptors whose signaling control cellular processes of cell proliferation, survival, apoptosis, angiogenesis, remodeling, and repair of tissues. Polymorphisms in TLR genes can change the balance between pro and anti-inflammatory cytokines, modulating the risk of infection, chronic inflammation, and cancer. Although many studies have demonstrated the direct involvement of TLR signaling in the benefit of tumor cells in certain cancers, little is known about the influence of these gene polymorphisms on myeloproliferative neoplasms (MPNs). In this context, the objective of the study was to investigate a possible association between the TLR polymorphisms and the development of MPNs. 167 patients diagnosed with MPN and 222 healthy controls from the same region were evaluated. Genomic DNA was extracted and the TLR2 (rs5743708), TLR4 (rs4986790, rs4986791), TLR9 (rs5743836, rs187084) and JAK2V617F polymorphisms were genotyped by PCR-RFLP. The statistical analysis was performed by OpenEpi and SNPstat software. The JAK2V617F mutation was found in 68.32% of patients. TLR9-1486C/T CT genotype was less frequent in patients with polycythemia vera (PV) (OR 0.39, 95% CI 0.20-0.78, P = 0.025). When haplotype frequencies were analyzed, -1237T/-1486C (TLR9) was also less frequent in men (OR 0.58, 95% CI 0.36-0.94) and JAK negative men patients (OR 0.43, 95% CI 0.21-0.88). We can infer that the TLR9-1486 CT genotype could be associated with protection for PV and the TLR9-1237T/-1486C haplotype, protection for men, as well as for JAK negative men patients with MPN. There were no associations between TLR2 and TLR4 gene polymorphisms and MPN.

Keywords: Case–control study; Genetic polymorphisms; JAK2V617F; Myeloproliferative disorders; Toll-like receptors.

MeSH terms

  • Adult
  • Aged
  • Bone Marrow Neoplasms / genetics*
  • Bone Marrow Neoplasms / metabolism
  • Female
  • Haplotypes / genetics
  • Humans
  • Janus Kinase 2 / genetics*
  • Janus Kinase 2 / metabolism
  • Male
  • Middle Aged
  • Myeloproliferative Disorders / genetics
  • Polycythemia Vera / genetics
  • Polymorphism, Single Nucleotide / genetics
  • Primary Myelofibrosis / genetics
  • Thrombocythemia, Essential / genetics
  • Toll-Like Receptor 2 / genetics
  • Toll-Like Receptor 2 / metabolism
  • Toll-Like Receptor 4 / genetics
  • Toll-Like Receptor 4 / metabolism
  • Toll-Like Receptor 9 / genetics*
  • Toll-Like Receptor 9 / metabolism
  • Toll-Like Receptors / genetics*
  • Toll-Like Receptors / metabolism


  • TLR2 protein, human
  • TLR4 protein, human
  • TLR9 protein, human
  • Toll-Like Receptor 2
  • Toll-Like Receptor 4
  • Toll-Like Receptor 9
  • Toll-Like Receptors
  • JAK2 protein, human
  • Janus Kinase 2