@article{29708,
  keywords = {leprosy, Chemokine serum production, Cytokine, Polymorphism analysis, TLR, Brazil},
  author = {Lima Santana N and Rêgo JL and Oliveira JM and Almeida LF and Braz M and Machado LMM and Machado P and Castellucci CLéa},
  title = {Polymorphisms in genes TLR1, 2 and 4 are associated with differential cytokine and chemokine serum production in patients with leprosy.},
  abstract = {<p><strong>BACKGROUND: </strong>Leprosy or hansen's disease is a spectral disease whose clinical forms mostly depends on host's immune and genetic factors. Different Toll-like receptors (TLR) variants have been described associated with leprosy, but with some lack of replication across different populations.</p>

<p><strong>OBJECTIVES: </strong>To evaluate the role of polymorphisms in genes TLR1, TLR2 and TLR4 and susceptibility to leprosy in a genetic case control study; to verify the association between genotypes of these markers and the immunological profile in the serum of patients with leprosy.</p>

<p><strong>METHODS: </strong>Pre-designed TaqMan® assays were used to genotype markers at TLR1 (rs4833095, rs5743551), TLR2 (rs7656411, rs3804099) and TLR4 (rs1927914, rs1927911). A panel of cytokines and chemokines was accessed by enzime-linked immunosorbent assay (ELISA) test in the serum of a subgroup of patients with and without leprosy reactions.</p>

<p><strong>FINDINGS: </strong>Our results show an association between the T allele of rs3804099 at the TLR2 gene and increased risk for leprosy per se [Odds ratio (OR) = 1.296, p = 0,022]. In addition, evaluating the association between different genotypes of the TLR1, 2 and 4 markers and cytokine/chemokine serological levels, IL-17 appears as an immunological marker regulated by the polymorphism of the three TLR genes evaluated, whereas different TLR1 genotypes were associated with differential production of IL-12p40 and MCP-1(CCL2). Furthermore, other relevant serum markers such as CXCL-10 and IL-6 seemed to be regulated by TLR2 variants and IL-1β was related to TLR4 genotypes.</p>

<p><strong>MAIN CONCLUSIONS: </strong>All together our data points that the tested TLR markers may have a regulatory role in the immunity against Mycobacterium leprae, by driving the host's production of key cytokines and chemokines involved in the pathogenesis of this disease.</p>
},
  year = {2017},
  journal = {Memorias do Instituto Oswaldo Cruz},
  volume = {112},
  pages = {260-268},
  issn = {1678-8060},
  url = {http://www.scielo.br/pdf/mioc/v112n4/0074-0276-mioc-0074-02760160366.pdf},
  doi = {10.1590/0074-02760160366},
  language = {eng},
}