The role of single nucleotide polymorphism TLR4 in the development of the non-alcoholic fatty liver disease in children

Abstract

Background. The TLR4 non-synonymous single nucleotide polymorphism (SNPs) changes the spatial structure and, probably, the sensitivity of the receptor to its ligands, determines the certain functional aberrations that can affect the nature and activity of inflammation. The purpose of the study was to exa­mine the associations of the SNP Asp299Gly rs4986790 of the TLR4 gene with liver structural changes, innate immunity, and carbohydrate metabolism parameters in children with NAFLD. Materials and methods. The study included 76 children with overweight and obesity aged 9 to 17 years. The presence of liver steatosis was determined using transient elastometry. According to the presence of liver steatosis, the children were divided into 2 groups; following the presence of SNP Asp299Gly (rs4986790) of the TLR4 gene, each group was divided into two subgroups: children with normal (Asp299Asp) and polymorphic (Asp299Gly) variants of the TLR4 gene. The blood serum content of insulin, IL-6, IL-10, TNF-α was determined by enzyme immunoassay, the HOMA-IR index was calculated. Results. The SNP Asp299Gly rs4986790 of the TLR4 gene detection rate in the heterozygous state among all children was 15.8 %, in children with NAFLD — 20.0 %, and in children without steatosis — 11.1 % (p > 0.05). Significant differences in the stiffness and degree of fatty liver in patients with AA and AG SNP rs4986790 genotypes were not found (p > 0.05). In children with NAFLD with the Asp299Gly variant of the TLR4 gene, the level of IL-10 was significantly higher compared to patients with the Asp299Asp variant of the TLR4 gene. At the same time, in children with the Asp299Asp variant without liver steatosis, a significantly higher level of IL-6 concentration was observed (p 0.05). A direct correlation was found between the level of IL-6 and insulin (r = 0.398; p < 0.01), the HOMA-IR index (r = 0.364; p < 0.05) in children with NAFLD. Conclusions. Children with NAFLD and SNP Asp299Gly rs4986790 TLR4 are characterized by significantly higher levels of IL-10 production and lower levels of insulin and HOMA-IR, which may indicate the protective properties of the SNP Asp299Gly rs4986790 TLR4 in the NAFLD development and progression.

Keywords

• single nucleotide polymorphism
• toll-like receptor 4
• non-alcoholic fatty liver disease
• children