Avaliação de polimorfismos em genes das citocinas IL-6 e IL-10 em pacientes portadores da neoplasia mielodisplásica

Abstract

Myelodysplastic Neoplasm is classified as a heterogeneous group of hematological disorders, characterized by ineffective hematopoiesis. Cytopenias, affecting one or more hematopoietic lineages, are commonly observed. This clonal pathology primarily affects older individuals, with approximately 80% of affected patients being above 65 years of age. The disease exhibits a wide range of progression factors, and immune alterations have been described at both the cellular and humoral levels. Immune checkpoints play a crucial role in regulating the pathways that establish stimulatory and inhibitory signals to mediate the immune response. However, several neoplasms can evade this surveillance, creating a complex scenario of immune system dysregulation. Dysregulation of the immune system can be triggered by the presence of polymorphic variants in genes involved in the activation of the innate immune cascade. Polymorphic variants in anti-inflammatory cytokine genes, which control the immune system, may also be relevant in patients with Myelodysplastic Neoplasm. In this context, the objective of this study was to evaluate polymorphisms in the IL-6 and IL-10 cytokine genes in Myelodysplastic Neoplasm, contributing to the elucidation of the presence or absence of an association between these polymorphisms and prognostic variables. This was a cross-sectional, analytical study involving 44 patients diagnosed with MDS based on clinical and laboratory criteria between 2008 and 2023, with a mean age of 70.45 years. The majority of participants were male, and there were 145 healthy controls matched by genotype. Qualitative PCR and allele discrimination assays for the rs1800795 and rs1800896 polymorphisms were performed on collected DNA samples. Statistical analyses were conducted using SPSS software version 20, with p-values <0.05 considered statistically significant. For IL6, the polymorphic G allele was more frequently present in patients diagnosed with MDS (84.09%) compared to controls (71.59%). Regarding genotype presence, a significant association was observed, through the chi-square test, between different genotypes and the number of cytopenias (-1,2,3) (p=0.002). There was also a significant association between different genotypes and the presence or absence of dysgranulopoiesis (p=0.034), as well as a significant association between different genotypes and neutrophil count (<0.8, ≥0.80) (p=0.036). For other genetic association models, no significant results were found, leading to the conclusion that there was no significant association of this polymorphism with the other variables in MDS for the study population. For the IL10 gene, genetic association models did not reveal any significant associations, indicating no significance between the presence of the polymorphism and the clinical and laboratory variables for MDS in the studied population.