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Polymorphisms in the TOLLIP Gene Influence Susceptibility to Cutaneous Leishmaniasis Caused by Leishmania guyanensis in the Amazonas State of Brazil

2015; Public Library of Science; Volume: 9; Issue: 6 Linguagem: Inglês

10.1371/journal.pntd.0003875

ISSN

1935-2735

Autores

Felipe Jules de Araújo, Luan Diego Oliveira da Silva, Tirza Gabrielle Ramos de Mesquita, Suzana Kanawati Pinheiro, Wonei de Seixas Vital, Anette Chrusciak‐Talhari, Jorge Augusto de Oliveira Guerra, Sinésio Talhari, Rajendranath Ramasawmy,

Tópico(s)

Synthesis and Biological Evaluation

Resumo

Introduction The clinical outcome to Leishmania-infection is determined by the individual adaptive immune T helper cell responses and their interactions with parasitized host cells. An early development of a proinflammatory immune response (Th1 response) is necessary for Leishmania-infection resolution. The Toll-interacting protein (TOLLIP) regulates human Toll-like receptors signaling pathways by down regulating the proinflammatory cytokines interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-α) and inducing the ant-inflammatory cytokine interleukin-10 (IL-10). Polymorphisms in the TOLLIP gene are associated with infectious diseases. Material and Methods The polymorphisms rs5743899 and rs3750920 in the TOLLIP gene were genotyped by polymerase chain reaction and restriction fragment length polymorphism (RFLP) analysis in 631 patients with cutaneous leishmaniasis (CL) caused by L. guyanensis and 530 individuals with no history of leishmaniasis. Results The G and T alleles of the rs5743899 and rs3750920 were more common in patients with CL than in healthy individuals (P = 2.6 x10-8 ; odds ratio [OR], 1.7 [ 95% confidence interval (CI) 1.4–2.0] and P = 1.9 x10-8 ; OR, 1.6 [95% CI 1.4–1.9] respectively). The r2 and D' linkage disequilibrium between the two polymorphisms are 0.05 and 0.473 with a confidence bounds of 0.37 to 0.57 respectively. Conclusion The two polymorphisms are independently associated with an increased risk of developing CL.

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