Associação de polimorfismos dos genes IL1B, IFNG e níveis de citocinas com a suscetibilidade a Leishmaniose Cutânea causada por Leishmania guyanensis

Abstract

Cutaneous Leishmaniasis caused by Leishmania species, present an important health problem, as significant morbidity and also lethality of the most severe cases of the disease. Different clinical studies and experimental have related the involvement from inflammatory cytokines in the development of CL. Feactures of CL pathogenicity to be associated with as host immunogenetics components to determine for the outcome of the disease. We investigated whether single nucleotide polymorphisms in IL1B, IL1RN and IFNG may be associated with elevated or decreased risk in the development of the CL. Nucleotide sequencing and PCR-RFLP were performed in 881 patients with CL and 837 controls. Circulating plasma cytokines were also assayed between CL patients and control subjects. The cytokine levels of IL-1β, IL-6, IL-8, MCP-1 and IFN-γ were significantly higher in patients compared to controls (p < 0.0001), levels elevated of IL-1ra were observed among the controls. IL1B and IFNG polymorphisms are associated with CL and cytokine levels. The IL1B rs16944 C/C genotype is related with lower levels of IL-1ra and associated with susceptibility to CL (OR=1.5 [95%CI 1.1–2.0]; p=0.004). Different SNPs and microsatellite of the IFNG gene were associated with protection and susceptibility to CL, those rs2069705 T and rs2430561 T were associated for the risk to CL (OR=1.5 [95%CI 1.2-2.0]; p=0.0004 / OR=1.4 [95%CI 1.2-1.6]; p=0.0002). IFNG alleles related with risk to CL are combined into haplotype (H1), this associated with susceptibility to CL (OR=1.7 [95%CI 1.2-2.2]; p=5x10-5) and related with lower levels of IFN-γ. Although, SNPs present in IL1B and IFNG may mark to the development of CL caused by Leishamania guyanensis, genetic variants are associated with the production of the IL-1β, IL-1Ra and IFN-γ.