Study of association of the polymorphism rs1799883 of the <i>FABP2</i> gene in children with bronchial asthma associated with obesity

Abstract

Introduction. Currently, there is a separate phenotype “bronchial asthma – obesity”, manifested by a more severe course of the disease, low rates of achieving asthma control, resistance to basic therapy. Asthma, like obesity, is recognized as a classic example of multifactorial diseases, which are based on a rather complex gene network. The active search for genetic markers characterizing individual characteristics of human metabolism continues. Of particular interest are the genes involved in the regulation of fat and carbohydrate metabolism.Aim. Analysis of associations of polymorphic loci Ala54Thr (G163A) of the FABP2 gene with bronchial asthma of varying severity and control of asthma in children.Materials and methods. 161 children with bronchial asthma in remission were examined by a continuous sampling method, of which 59 patients with obesity of 1-3 degrees without concomitant endocrine pathology. The examination included general clinical, functional, and instrumental methods. The level of asthma control was determined according to the GINA criteria (2018). The biochemical study was carried out on an automatic analyzer SAPPHIRE 400 (Japan). The study of gene polymorphisms was carried out by real-time polymerase chain reaction using sets of “Metabolism” (Research and Production Company “Litekh”, Moscow) on the CFX-96 Biorat device (USA).Results. We have not identified associations of the presence of polymorphic loci of the FABP2 gene with obesity. It was determined that in children with bronchial asthma, the frequency of carrying the homozygous genotype Thr/Thr and the minor allele Thr increased by 1.5 times compared to the control group (OR 9.043; 95%CI [2,093–39,073], p=0.0011 and OR 2.946; 95%CI [1,698‒5,111], p=0.001, respectively), and in children with bronchial asthma with and without asthma control, the carriage of the homozygous Thr/Thr genotype and the rare A allele increased the risk of uncontrolled bronchial asthma (OR 2.42; 95%CI [1.23‒4.79], p=0.03 and OR 1.75; 95%CI [1,119‒2,736], p=0.01), the frequency of the homozygous Ala/Ala genotype and the frequent Ala allele was detected 1.5 times more often in children with bronchial asthma associated with obesity (OR 2.176; 95%CI [1.001‒4.727], p=0.0008 and OR 2.378; 95%CI [1.495‒3.780], p=0.0002, respectively).Conclusion. Although we have not identified associations of the presence of polymorphic loci of the FABP2 gene with obesity, it has been shown that children with Ala54Thr+Thr54Тhr genotypes have significantly higher glucose levels (4.9±0.06 mmol/L compared with carriers of the Ala54Ala genotype 4.0±0.06 mmol/L, p<0.001), cholesterol (4.8±0.4 mmol/L compared with carriers of the Ala54Ala genotype 3.93±0.1 mmol/L, p<0.05) and low density lipoproteins (2.55±0.09 mmol/L compared with carriers of the Ala54Ala genotype 2.26±0.1 mmol/L, p<0.05). There is an obvious need for further investigation of the effect of gene polymorphism on the indicators of carbohydrate and lipid metabolism, depending on the nature of diets. These issues require further study as part of the search for probable cause-and-effect relationships and the creation of personalized programs depending on polymorphic gene variants.