PREDICTING THE PROBABILITY OF DEVELOPING OBESITY DEPENDING ON LEPTIN AND LEPTIN RECEPTOR POLYMORPHISMS

Abstract

Introduction. Metabolic syndrome is a heterogeneous pathological condition that combines different stages of obesity, impaired glucose tolerance, atherogenic dyslipidemia and arterial hypertension. Obesity itself is a key element of this syndrome. Hormonal disorders, the central one of which is insulin resistance, trigger a cascade of neuroendocrine changes that lead to the progression of MetS. Monogenic mutations are often detected in patients with severe obesity, as well as with early (up to 10 years) its debut. In recent years, it has been increasingly investigated for a genetically determined breakdown in the mechanism of leptin's influence on the development of obesity. The aim of this study – to evaluate the probability of obesity development in patients with LEP and LEPR polymorphisms in Ukrainian population. Research Methods. 53 obesity and 43 non-obesity patients underwent genotyping of the LEP and LEPR genes (K109R (rs1137100), Q223R (rs1137101), K656N (rs1805094), G2548A (rs7799039)) polymorphism was performed using TaqMan™ SNP Genotyping Human Assays (Thermo Fisher Scientific, USA).  Results and Discussion. Comparing rs1137101 Allele A, rs1137101 Allele G statistically significant differences were revealed, while comparing rs1805094 Allele C, rs1805094 Allele G, rs7799039 Allele A, rs7799039 Allele G, rs1137100 Allele A, rs1137100 Allele G depending on group indicated no statistically significant differences. SNP (rs1137101) Allele A statistically significant differences depending on obesity degree (p < 0.001). Comparing the rest of SNP`s Allele`s (rs1805094 Allele C, rs1805094 Allele G, rs7799039 Allele A, rs7799039 Allele G, rs1137101 Allele G, rs1137100 Allele A, rs1137100 Allele G, rs696217 Allele G) no statistically significant differences was noted. Prediction of the probability of developing obesity depending on the polymorphism of leptin and leptin receptors revealed the dependence of only mutations in LEPR (Q223R (rs1137101)) in the Ukrainian population. According to the results of the ROC analysis sensitivity and specificity of the method were 65.5 % and 67.8 %, respectively. Conclusions. Our analysis showed that LEPR Q223R (rs1137101) polymorphism could be a potential genetic risk factor for obesity in Ukrainian population regardless of the homozygous or heterozygous genotype (genotypes AA, AG, GG). At the same time, allele A was found in 70.83 % of cases of patients with 2nd and 3rd degree obesity. And homozygous AA and GG genotypes in 24.5 % and 28.3 %, respectively. The results obtained can be used in the practice for early diagnosis of different types of obesity and for prognosing of results of bariatric surgery.