title: Polymorphisms in the TOLLIP Gene Influence Susceptibility to Cutaneous Leishmaniasis Caused by Leishmania guyanensis in the Amazonas State of Brazil.
abstract: BACKGROUND
  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.
  
  
  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.
  
  
  CONCLUSIONS
  The two polymorphisms are independently associated with an increased risk of developing CL.
authors.affiliation: Faculdade de Medicina, Universidade de Nilton Lins, Manaus, Amazonas, Brazil.
authors.forename: Felipe Jules
authors.initials: FJ
authors.lastname: de Araujo
authors.affiliation: Faculdade de Medicina, Universidade de Nilton Lins, Manaus, Amazonas, Brazil.
authors.forename: Luan Diego Oliveira
authors.initials: LD
authors.lastname: da Silva
authors.affiliation: Fundação de Medicina Tropical Dr. Heitor Vieira Dourado, Manaus, Amazonas, Brazil.
authors.forename: Tirza Gabrielle
authors.initials: TG
authors.lastname: Mesquita
authors.affiliation: Fundação de Medicina Tropical Dr. Heitor Vieira Dourado, Manaus, Amazonas, Brazil.
authors.forename: Suzana Kanawati
authors.initials: SK
authors.lastname: Pinheiro
authors.affiliation: Faculdade de Medicina, Universidade de Nilton Lins, Manaus, Amazonas, Brazil.
authors.forename: Wonei de Seixas
authors.initials: Wde S
authors.lastname: Vital
authors.affiliation: Fundação de Medicina Tropical Dr. Heitor Vieira Dourado, Manaus, Amazonas, Brazil.
authors.forename: Anette
authors.initials: A
authors.lastname: Chrusciak-Talhari
authors.affiliation: Fundação de Medicina Tropical Dr. Heitor Vieira Dourado, Manaus, Amazonas, Brazil.
authors.forename: Jorge Augusto de Oliveira
authors.initials: JA
authors.lastname: Guerra
authors.affiliation: Faculdade de Medicina, Universidade de Nilton Lins, Manaus, Amazonas, Brazil.
authors.forename: Sinésio
authors.initials: S
authors.lastname: Talhari
authors.affiliation: Faculdade de Medicina, Universidade de Nilton Lins, Manaus, Amazonas, Brazil; Fundação de Medicina Tropical Dr. Heitor Vieira Dourado, Manaus, Amazonas, Brazil.
authors.forename: Rajendranath
authors.initials: R
authors.lastname: Ramasawmy
mesh_terms: D000293:Adolescent; D000328:Adult; D001938:Brazil / Q000453:epidemiology; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics*; D018334:Leishmania guyanensis / Q000187:drug effects / Q000235:genetics* / Q000302:isolation & purification; D016773:Leishmaniasis, Cutaneous / Q000453:epidemiology / Q000469:parasitology*; D015810:Linkage Disequilibrium; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D015398:Signal Transduction; D055815:Young Adult
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; C410602:TOLLIP protein, human