Evaluation of the involvement of PPARG2 gene rs1801282 polymorphism in the pathogenesis of bronchial asthma with obesity in children

Abstract

Introduction. Features of the clinical course of bronchial asthma in children with obesity made it possible to identify a special phenotype, when the presence and severity of obesity determine a more severe course of asthma and a worse response to asthma therapy. Asthma, like obesity, is recognized as a classic example of multifactorial diseases, which are based on a rather complex gene network. Studying the genetic basis of both of these complex traits and linking them to the asthma phenotype should contribute to our understanding of the overall genetic basis of these pathological disorders.Aim. Evaluation of the clinical and genetic significance of the rs1801282 polymorphism of the PPARG2 gene (34C>G, p.Pro12Ala) in children with asthma and obesity.Materials and methods. 161 children with asthma were examined, including 59 patients with obesity 1-3 degrees. The examination included general clinical, functional, instrumental methods. The level of asthma control was determined according to the GINA criteria (2018). The study of gene polymorphisms was carried out by the real-time polymerase chain reaction.Results. An analysis of the frequencies of the PPARG2 gene polymorphism in children with bronchial asthma did not reveal any differences from the control group healthy people. In 61% of children with asthma and obesity, there was no control over the disease, which was associated with the G allele (OR 2.4 [95% CI: 1.09‒5.30], p=0.0281). An increase in the activity of lactate dehydrogenase and a decrease in the membrane potential of mitochondria in peripheral blood lymphocytes in children with the GG genotype were revealed, which may indirectly affect the level of disease control.Conclusion. The comorbidity of asthma and obesity in children affects the control of the disease. This manifests itself through immune mechanisms that play a key role in energy homeostasis and mitochondrial dysfunction of immunocompetent blood cells. The G-allele of the PPARG2 gene can be a marker of the lack of control over the disease in obese children with asthma. The pathogenetic significance of this polymorphism requires further study.