Association of leptin receptor gene polymorphisms and meta-inflammation markers with metabolically unhealthy obesity in children

Abstract

The aim: to study the contribution of single-nucleotide polymorphisms (SNP) of the leptin receptor (LEPR) gene and meta-inflammation markers to the formation of metabolically unhealthy obesity (MUO) in children. Materials and methods. A total of 109 obese children aged 6–18 years were examined. Based on the recommendations of the National Heart, Lung, and Blood Institute (NHLBI), 2 observation groups were formed. The main group (n = 56) was represented by patients with MUO. The control group (n = 53) comprised children with metabolically healthy obesity (MHO). Serum levels of interleukin-1β (IL-1β) were measured using a chemiluminescent immunoassay (CLIA) method, interleukin-6, leptin, adiponectin – by enzyme-linked immunosorbent assay (ELISA) and the serum level of C-reactive protein were quantified by latex turbidimetric method (Synevo, Ukraine). The method of next-generation sequencing (NGS) (CeXGat, Germany) was used to identify LEPR SNP. Statistical methods were used: analysis of variance, Spearman’s correlation analysis and multiple discriminant analysis. Results. In obese children aged 6 to 18 years, there was an increase in pro-inflammatory adipokines IL-6 and leptin and a decrease in anti-inflammatory adiponectin. Statistically significant changes in these indicators were more expressed in the main group: IL-6 – 7.4 ± 0.5 pg/ml (ρ = 0.65; P ≤ 0.001); adiponectin – 3.9 ± 0.8 μg/ml (ρ = -0.27; P = 0.007) among all the children examined, leptin in girls – 47.8 ± 4.4 ng/ml (ρ = -0.28; P = 0.003) compared with the results of patients in the control group: IL-6 – 4.3 ± 0.3 pg/ml, adiponectin – 7.7 ± 2.4 μg/ml, leptin in girls – 32.5 ± 4.3 ng/ml, P ≤ 0.05. The most important in the development of MUO were the following SNP of the LEPR gene: rs3790435 (CiMUO = 0.939), rs2186248 (CiMUO = 0.862), P < 0.05. A strong correlation was found between MUO and serum IL-6 level (ρ = 0.7), LEPR SNP rs3790435 (ρ = 0.7), basal hyperinsulinemia (ρ = 0.72); Р ≤ 0.001. The risk of IL-6-dependent meta-inflammation in the presence of SNP rs3790435 of the LEPR gene: OR = 17.11; 95 % CI 2.8–20.4. Conclusions. Meta-inflammation in MUO is IL-6-dependent. Among the 10 SNPs of the LEPR gene that we identified, SNP rs3790435 of the LEPR gene has a strong association with the formation of MUO. SNP rs2186248 LEPR was described by us for the first time when it was found in 94.1 % of obese children, but it was characterized by the presence of a weak association with MUO.