Іnfluence of the rs1800795 (-­174G/C) polymorphism of the interleukin-­6 gene on the risk clinical and metabolic manifestations of hypothalamic dysfunction in children and adolescents

Abstract

Objective — to determine the role of the rs1800795 (-174G/C) polymorphism of the interleukin-6 (IL-6) gene in the development of clinical and metabolic manifestations of hypothalamic dysfunction (HD) in children and adolescents. Materials and methods. Genotyping was performed in 40 children (aged (14.97 ± 2.07) years) from the Ukrainian population with HD and obesity. The rs1800795 (-174G/C) polymorphism of the IL-6 gene was determined using polymerase chain reaction, restriction fragment length polymorphism (PCR-RFLP) analysis followed by agarose gel electrophoresis. Results and discussion. The obtained results indicate the involvement of the IL­-6 gene polymorphism rs1800795 (-­174G/C) — specifically its G allele — in the development of clinical and metabolic manifestations of HD in children and adolescents, primarily obesity, insulin resistance (IR), atherosclerotic changes, carbohydrate metabolism disorders, and metabolic dysfunction­associated steatotic liver disease (MASLD). The presence of the G allele in both heterozygous (C/G) and homozygous (G/G) states was associated with the progression of obesity, IR, increased glycated hemoglobin levels, elevated markers of atherogenic dyslipidemia, and increased aspartate aminotransferase and alanine aminotrans­ferase activity; this points to liver tissue involvement (development of MASLD) against the background of neuroendo­crine disorders. For the first time, a pronounced inverse correlation was identified between the presence of the G allele and serum 25(OH)D levels. Geographic and racial differences may influence the association between IL-­6 gene polymorphisms and endocrine disorders, explaining the inconsistent effects of these polymorphisms and their role in disease development across different populations. Conclusions. The presence of the G allele (especially in the homozygous G/G state) in patients with hypothalamic pathology is associated with a deterioration of key metabolic parameters. A distinct allele­specific effect is observed: an increase in body weight, progression of insulin resistance, development of atherogenic dyslipidemia, elevation of liver cytolysis markers, and worsening vitamin D deficiency; this indicates the significant pathogenetic role of this polymor­phism in the development of metabolic syndrome associated with hypothalamic pathology.