Polimorfismo genético, metilação e expressão do gene IL6 em crianças com obesidade

Abstract

Obesity is a common, complex, non-malignant disease that develops due to interactions between genes and the environment. The increase in cell size (hypertrophy) alters the functioning of adipose tissue, secretion and sensitivity to signaling molecules, such as inflammatory and hormonal factors. Among the secreted inflammatory factors, Interleukin-6 (IL-6) stands out, an important pleiotropic cytokine active in immunity, hematopoiesis, insulin sensitivity and energy homeostasis. Modulation of IL6 gene expression is the result of genomic modifications, such as genetic polymorphisms, and epigenetic mechanisms. The rs1800795 polymorphism is the most commonly studied in the IL6 gene, it is found at position -174 of the promoter region of the gene and is characterized by the exchange of a G (guanine) for a C (cytosine). This polymorphism is associated with the development of DM2 and obesity. DNA methylation is an epigenetic modification involved in the regulation of gene expression, usually via gene silencing, which contributes to the risks of many multifactorial diseases such as T2DM, cardiovascular disease and obesity. This study aims to evaluate the occurrence of the rs1800795 polymorphism, the methylation pattern and the expression of the IL-6 gene and associate them with the clinical and anthropometric parameters of Brazilian children with obesity and eutrophy. Biochemical parameters (fasting blood glucose, HDL, LDL and insulin) were evaluated in serum using a colorimetric enzymatic assay. The rs1800795 polymorphism was evaluated using the polymerase chain reaction (PCR) technique, followed by restriction enzyme treatment. DNA methylation in the promoter region of the IL6 gene was analyzed by the methylation-specific PCR (MSP) technique. IL-6 expression was assessed by flow cytometry. The frequencies of genotypes and alleles related to the genetic polymorphism rs1800795 did not differ between groups. The presence of the C allele was associated with increased fasting glucose and decreased waist circumference in the obese group, and increased insulin in the control group. MSP analyzes detected loss of methylation in the IL6 gene in children with obesity, and this result correlated with fasting glucose levels. The percentage of cells expressing IL-6 was increased in the obese group and correlated with levels of fasting glucose, HDL and waist circumference. Together, the results suggest a relevant role for IL-6 in childhood obesity, as well as mechanisms related to its gene transcription.