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

<div><p>Introduction</p><p>The clinical outcome to <i>Leishmania</i>-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 <i>Leishmania</i>-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 <i>TOLLIP</i> gene are associated with infectious diseases.</p><p>Material and Methods</p><p>The polymorphisms rs5743899 and rs3750920 in the <i>TOLLIP</i> gene were genotyped by polymerase chain reaction and restriction fragment length polymorphism (RFLP) analysis in 631 patients with cutaneous leishmaniasis (CL) caused by <i>L</i>. <i>guyanensis</i> and 530 individuals with no history of leishmaniasis.</p><p>Results</p><p>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.</p><p>Conclusion</p><p>The two polymorphisms are independently associated with an increased risk of developing CL.</p>