Evaluation of treatment effectiveness of asthma/COPD overlap in patients with and without obesity considering the polymorphic variant C646G of the NR3C1 gene (rs41423247)

Abstract

The Aim. The current study evaluates the possibility of using the C646G polymorphic variant of the NR3C1 gene (rs41423247) for the personalized administration of combination therapy with inhaled glucocorticosteroids (iGCs) and long-acting β2-agonists in patients with asthma/COPD overlap (ACO) with and without obesity.Material and methods. Forty patients with ACO were included (17 patients with BMI < 30 and 23 with obesity (BMI ≥ 30) to received combined treatment with the use of prolonged β 2 -agonists and ICS. The CAT test, the asthma control questionnaire (Asthma Control Questionnaire-5 - ACQ-5) and the BODE index were used to analyze treatment outcomes, with genetic markers being considered one month after the study began. To assess the distribution of genotypes and alleles between groups, we used the two-tailed Pearson chi-square test (χ2) and the odds ratio (OR) in the 95% confidence interval (CI). Mathematical processing of the obtained data was performed using the SPSS (Statistical Package for Social Science Statistics) 16,0 programs.Results. The analysis of the obtained results revealed that a significant frequency of the GG genotype (80,00%) was observed in the group of patients who noted progressive deterioration of the symptom according to the CAT test, which significantly differed [χ²=17,293; p˂0,001] from that in the group of patients with positive CAT dynamics, in whom the GG genotype did not occur at all. In patients with no improvement on the CAT scale, the rate of the G allele was 0,96, and the rate of the C allele was 0,44; in patients with positive dynamics on the CAT scale, these numbers were 0,4 and 1, respectively [χ²=7,721; p=0,006; BP=5,000; 95% CI: 1,547-16,163]. The results of analyzing the dynamics of the number of points obtained for the ACQ-5 were comparable to those obtained when the CAT test was evaluated. The GG genotype was found in 50,00% of patients with negative or complete absence dynamics of the BODE index, compared with 12,5% of patients with positive dynamics [χ2=5,943, р=0,015; ВР=7,000 (95 % ДІ: 1,300-37,705)]. In the group of ACO patients with obesity, 94,44% of patients with negative or absent BODE index dynamics were carriers of the G allele [χ2=8,074, р=0,005], whereas in the group of ACO patients with normal/overweight body weight, all patients with the GG genotype had negative BODE index dynamics [χ2=6,679; р=0,016]. The GG genotype was found in 59,1% of patients with negative and absent dynamics of the BODE index, but not in any patient with positive dynamics of the BODE index [χ2=12,472, р˂0,001; ВР=24,556 (95 % ДІ: 2,752-219,100)]. Among the ACO patients studied, we identified 14 people with the GG genotype for the NR3C1 gene (rs41423247), 13 of whom (92,85%) had zero or negative dynamics of the condition in combined therapy with ICS and long-acting 2 agonists, according to the BODE index estimate. When the changes in the BODE index in non-obese patients (BMI˂30) were studied when the long-acting β 2 -agonists + ICS regimen was used, four of seventeen patients had negative BODE index dynamics: two with the CG genotype and two with the GG genotype [χ2=3,767, р=0,05]. In the presence of the GG genotype, patients with ACO and obesity (BMI≥30) experienced a progressive course of the disease or zero dynamics in response to the prescribed treatment. Simultaneously, according to the BODE index, there were no patients in the same group with the GG genotype for the NR3C1 (rs41423247) gene who had positive dynamics in response to treatment [χ2=5,856, р=0,016].Conclusions. The study's findings show that the number of people with the GG genotype for the NR3C1 gene (rs41423247) is significantly higher in patients with ACO and obesity than in patients with ACO and normal/overweight body weight. The GG genotype of the NR3C1 gene (rs41423247) is associated with negative dynamics in the application of combined therapy of ICS and long-acting 2-agonists, and can serve as a prognostic marker for assessing the risk of lack of effect from therapy according to this scheme prior to its initiation in patients with ACO, particularly in the presence of ACO and obesity comorbidities.