Variante do gene TREM1 em indivíduos com leishmaniose cutânea no estado do Amazonas, Brasil: um estudo caso-controle

Abstract

Leishmaniasis is a group of chronic infectious diseases caused by protozoan of the genus Leishmania transmitted by phlebotomine bites. The broad spectrum of clinical manifestations ranges from mild cutaneous lesions that may be self-healing to severe mucosal or visceral lesions. Cutaneous Leishmaniasis (CL) is the most common form and affects millions of people worldwide. The clinical outcome of CL is influenced by host-specific T cell responses. The Triggering Receptor Expressed on Myeloid Cells (TREM)-1 is a potent amplifier of inflammatory signal and belongs to the superfamily of immunoglobulin expressed on the neutrophils and monocytes surface. The TREM-1 pathway results in the degranulation of neutrophils, calcium influx, cell survival and overwhelming cytokine production. The TREM1 gene is localized in the chromosome 6. In this study we investigated whether the TREM-1 polymorphism rs22344237 is associated with CL caused by Leishmania guyanensis in the Amazonas. We also checked whether this polymorphism has any influence in the expression of several plasma cytokines IL-1β, IL-6, IL-8, IL-10 and TNF-α. In this case-control study, we analyze a polymorphic variant rs2234237 A / T (Ser25Ter) of the TREM1 gene by Polymerase Chain Reaction - Restriction Fragment Length Polymorphism (PCR-RFLP) in 778 patients with CL and 766 healthy controls. Plasma cytokines IL-1β, IL-6, IL-8, IL-10 and TNF-α were measured in 374 healthy controls by Luminex. The Hardy-Weinberg equilibrium was verified and χ2 and odds ratio (OR) test with a 95% confidence interval (CI) was used to compare the alleles and genotypes frequencies among the case and control groups. ANOVA non-parametric test was used to compare genotypes over cytokines concentrations. Hardy Weinberg equilibrium was observed in both cases and controls. Similar frequency of genotypes was also observed between cases and controls suggesting that this polymorphism do not play a role in susceptibility to CL. Similarly, the different genotypes did not show any correlation with the levels of the different cytokines. Altogether the lack of association to CL caused by L. guyanensis in the Amazonas do not rule out the role played by TREM 1 in the immune response to the disease. Other polymorphisms in the gene should be studied before ruling out the lack of association.