A polymorphism in the IL1B gene (rs16944 T/C) is associated with cutaneous leishmaniasis caused by Leishmania guyanensis and plasma cytokine interleukin receptor antagonist

Abstract

Nod-like Receptor Protein3 (NLRP3) inflammasome in macrophages infected with Leishmania sp. enhances the secretion of IL-1β. Excess IL-1β production is linked to disease severity in patients with cutaneous leishmaniasis (CL) caused by L. mexicana. Blockade of the NLRP3 inflammasome in cell cultures from skin biopsies of patients with CL caused by L. braziliensis inhibited the release of IL-1β. We hypothesized that common single nucleotide polymorphisms in the IL1B and in its receptor antagonist IL1RN genes may be predictive of CL caused by L. guyanensis. The SNPs -511T/C (rs16944) and +3954C/T (rs1143634) of the IL1B and IL1RN VNTR (rs2234663) were assessed in 881 patients with CL and 837 healthy controls by PCR-RFLP and direct PCR respectively. Plasma cytokines levels were also assayed. The plasma levels of IL-1β were higher in patients compared to control subjects. In contrast, increased plasma levels of IL-1Ra were observed in controls. The rs16944 C/C genotype was more common among the patients (OR = 1.5 [95%CI 1.1-2.0]; P = 0.004) and the C allele suggests susceptibility to CL (OR = 1.2 [95%CI 1.1-1.4]; P = 0.003). The rs16944 C/C genotype shows a tendency to correlate with lower levels of the IL-1Ra cytokine. Low levels of IL-1Ra cytokine and rs16944 C/C genotype seem to confer susceptibility to L. guyanensis-infection in the Amazonas.

Keywords: Amazonas; Cutaneous Leishmaniasis; Leishmania guyanensis; Single nucleotide polymorphism, Interleukin-1 beta and Interleukin-1 receptor antagonist.