Polymorphisms of the rs1042713 and rs1042714 genes of the β2-adrenergic receptor in children with bronchial asthma and obesity

   Introduction. The clinical features of asthma in individuals with high body weight have led to the identification of a specific phenotype: asthma in obese patients, where the presence and severity of obesity contribute to a more severe course of asthma and make it difficult to treat. Despite the increasing number of studies confirming the significance of the ADRB2 gene in the pathogenesis of asthma and obesity, the available data are rather contradictory and do not provide a definitive answer.

   Aim. Evaluation of the role of polymorphic variants rs1042713 and rs1042714 of the ADRB2 gene in children with BA and obesity.

   Materials and methods. A single-center observational cross-sectional pilot study was conducted on 161 children with a diagnosis of BA, with an average age of 12.6±0.2 years. The study participants were divided into two groups: the main group consisted of obese patients (n = 59), and the comparison group consisted of patients with normal body weight (n = 102). Genotyping was performed using the “Metabolism” kits from NPF “Litex” (Moscow) using the PCR-RV method on a CFX-96 Bio-Rad instrument (USA).

   Results. An increase in the frequency of detection of the 16Gly allele of the rs1042713 polymorphism in patients with asthma and obesity was shown (OR = 1.59; 95 % CI [1.01–2.50]). An association of the Gly16Gly genotype with an increased risk of uncontrolled BA in children with obesity was found (OR = 9,.68 [95 % CI = 1.16 –81.12]). In 59 % of cases, patients with mild asthma had the “wild” genotype Gln27Gln rs1042714 versus 37 % with moderate to severe disease (OR = 2.45, [95 % CI [1.23–4.91]) and the Gln allele (OR = 2.03, [95 % CI = 1.19–3.44]) the ADRB2 gene. The presence of polymorphic variants of the ADRB2 gene had a clinical implementation. Doses of topical glucocorticosteroids (TGCs) in children with obesity-related BA were significantly higher than in patients without obesity (250 [100—500] μg/day and 100 [0—250] μg/day. respectively, p = 0,0017) and were associated with the presence of the 16Gly allele of the rs1042713 polymorphism of the ADRB2 gene (Me 500 [250—750] μg/day, p = 0,0002) and the 27Glu allele of the rs1042714 polymorphism, which may be a potential predictive marker of response to inhaled corticosteroids in carriers of these ADRB2 genotypes in children with bronchial asthma.

   Conclusions. The presence of Arg16Gly and Gly16Gly genotypes and the Arg16 allele of the ADRB2 gene in patients with BA and obesity increases the risk of uncontrolled disease. The results obtained are important for identifying individuals at risk of uncontrolled BA in obese children, which allows for timely implementation of a set of preventive measures among them.

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