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

Autor: Rajendranath Ramasawmy, Sinésio Talhari, Anette Chrusciak-Talhari, Felipe Jules de Araújo, Tirza Gabrielle Ramos de Mesquita, Luan Diego Oliveira da Silva, Jorge Augusto de Oliveira Guerra, Wonei de Seixas Vital, Suzana Kanawati Pinheiro
Jazyk: angličtina
Rok vydání: 2015
Předmět:
Zdroj: PLoS Neglected Tropical Diseases
PLoS Neglected Tropical Diseases, Vol 9, Iss 6, p e0003875 (2015)
ISSN: 1935-2735
1935-2727
Popis: 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.
Author Summary Leishmaniasis is an infectious disease caused by the protozoan parasite of the Leishmania genus. It is transmitted by infected sandfly (the phlebotomines) and caused either visceral or tegumentary leishmaniasis depending on the species. In areas of endemicity for leishmaniasis, not all individuals exposed to the same environment develop the disease. It has been suggested that the genetic background of the individual may play a key role. The peri-rural regions of Manaus, the capital city of the Amazonas state of Brazil has become over the years endemic areas of mainly L. guyanensis American Tegumentary Leishmaniasis because of the constant deforestation and new settlements. Infected symptomatic patients most often develop localized cutaneous leishmaniasis (CL), characterized by a single or multiple well-demarcated cutaneous ulcer with raised borders and granulomatous center. In this study, we tried to understand why some individuals develop cutaneous leishmaniasis while other in the same area do not by genotyping two polymorphisms situated the TOLLIP gene and we saw that both polymorphisms are associated with cutaneous leishmaniasis.
Databáze: OpenAIRE
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