Obesity in Children with Leptin Receptor Gene Polymorphisms

Abstract

Introduction: The study of single nucleotide polymorphisms (SNPs) of the leptin receptor gene (LEPR) based on next generation genomic sequencing (NGS) data is becoming an increasingly important aspect of diagnosis, treatment and prevention of both metabolically healthy (MHO) and metabolically unhealthy obesity (MUO) phenotypes. Material and methods: 35 obese children 6-18 years old were examined by the NGS method with bioinformatic analysis. The main group (n = 18) was formed by children with MUO, according to the recommendations of the expert group of the National Heart, Lung, and Blood Institute. The control group (n = 17) was represented by children with MHO. Statistical methods were used: analysis of variance, Wald’s sequential analysis, Spearman’s correlation analysis, analysis of nominal data and multiple discriminant analysis. Results: 10 types of non-synonymous SNPs (rs3790435, rs1137100, rs2186248, rs70940803, rs79639154, rs1359482195, rs1137101, rs1805094, rs13306520, rs13306522) of the LEPR gene in obese children have been identified. Multiple discriminant analysis demonstrated that the following LEPR SNPs are of greatest importance in the development of MUO: rs3790435, rs13306522, rs13306520. Analysis of nominal data revealed significant differences in the groups for Copy number variation (CNV) rs3790435 of the LEPR gene. Wald’s analysis allowed us to identify 6 important predictors of MUO (І ≥ 0.5): 2 CNV rs3790435 (Relative Risk, RR = 2, Prognostic coefficient, PC = +2.76); male gender of the child (RR = 1.3, PC = +1.35); rs3790435 (RR = 1.9, PC = +2.76); hyperleptinemia more than 40.56 ng/ml (RR = 2, PC = +3); CNV rs1359482195 ≥ 3 (RR = 1.9, PC = +5.8); SNP of the LEPR gene ≥4 (RR = 3.8, PC = +5.8). Conclusion: Children with the genotype rs3790435 gene LEPR had signs of MUO more often.

Analysis of leptin, adiponectin and adiponectin gene polymorphism and leptin receptor in obese children and adolescents

“…However, the included studies on LEPR gene polymorphisms had inadequate samples resulting in inadequate statistical processing. Thus, the present negative results are still underpowered and further clarification may be obtained from studies with a larger number of subjects (24,25).…”

Асоціації Варіантів Гена GHRL Із Розвитком Ожиріння Та Метаболічних Порушень У Дітей

“…Over the past decades, due to the pandemic nature of the spread of obesity, the problem of its treatment and prevention of metabolic disorders in children has been in the focus of medical community [22]. Evidence has now been obtained that a sedentary lifestyle, excessive consumption of high-calorie foods, sleep disorders and genetic predisposition cause a high risk of developing polygenic obesity [2]. Mutations of genes involved in the regulation of appetite, of the activity of hedonic pathways, the formation of food preferences, carbohydrate and fat metabolism, as well as the development of adipocytes, the distribution of adipose tissue in the body may predetermine excessive accumulation of fat [1,4,16,32].…”

Association of rs1137101 with hypertension and type 2 diabetes mellitus of Mongolian and Han Chinese

“…Epidemiological studies have shown that HTN is a major risk factor for T2DM[ 7 ]. One-third of HTN patients also have T2DM and are at an increased risk of cardiovascular disease and mortality[ 8 , 9 ].…”

“…These predictions imply that the rs1137101 mutation may influence protein structure and have an impact on protein function. Previous studies have associated rs1137101 (Gln223Arg) with obesity, cancer, HTN and DM[ 9 , 19 , 20 ]. It also has been shown to be a risk factor for HTN and T2DM in the Chinese population[ 21 , 22 ].…”