A genetic variant associated with a poorer therapeutic response in patients with asthma may also be linked to more severe chronic obstructive pulmonary disease, researchers have found.
The polymorphisms at codons 16 and 27 of the beta-2-adrenoreceptor (ADRB2) gene are responsible for enhanced down-regulation of the beta-2-adrenoreceptor, and research suggests that Arg/Arg homozygosity at position 16 is associated with worse control of disease in patients with bronchial asthma.
However, the results of studies exploring the impact of this variant “on the clinical response to the administration of the beta-2-adrenoreceptor agonists in COPD patients are “parse and inconclusive,” according to Justyna Emeryk-Maksymiuk and colleagues at the Medical University of Lublin in Poland.
In a study published in the April issue of Pulmonary Pharmacology & Therapeutics, the researchers looked for variants of the ADRB2 gene in blood samples taken from 92 patients with stable grade COPD.
They collected data on each patient’s disease course during the previous 12 months, including the frequency of exacerbations requiring hospitalization, and antibiotic and systemic corticosteroid use.
They found significant differences between patients with either the Arg/Arg (n = 18), Arg/Gly (n = 61) and Gly/Gly (n = 13) polymorphism at codon 16 of the ADRB2 gene (Pulm Pharmacol Ther. 2017. doi: 10.1016/j.pupt.2017.01.005).
Those who were Arg/Arg homozygotes were significantly more likely to require two or more courses of antibiotic therapy: 33% of this group required two courses of antibiotics compared to 16.4% of those with the Arg/Gly polymorphism and none of those with the Gly/Gly polymorphism.
Those with the Arg/Arg polymorphism also required significantly more corticosteroid therapy; 16.7% needed three or more courses of systemic corticosteroid therapy, compared to none of the patients with the other polymorphisms.
However there were no significant differences between the three groups in the number of hospitalizations over the prior 12 months.
The researchers did not see any significant effects on hospitalizations, courses of corticosteroids or antibiotics from polymorphisms at codon 27 of the ADRB2 gene.
“The majority of researchers focus on the bronchodilator effect brought by the activation of the beta-2-adrenoreceptors, with less emphasis on the facts that these receptors are also involved in the inhibition of mast cell degranulation, chemotaxis, adhesion and activation of leukocytes, as well as in the improvement of mucociliary clearance of respiratory epithelium,” the authors wrote.
“The results of these studies confirmed that the Arg/Arg genotype at codon 16 predisposes patients to clinically more severe manifestation of obstructive respiratory disorders.”
The authors noted that the differences in the effect of genetic polymorphisms in the ADRB2 gene could also be the result of differences in the use of inhaled glucocorticoids, as these can prevent the desensitization of the beta-2-adrenoreceptor.
Previous research has found that nonusage of inhaled glucocorticoids in asthma patients with the Arg/Arg phenotype is associated with a twofold greater odds of uncontrolled asthma, when compared with patients with the Gly/Gly phenotype.
While patients with asthma are recommended to have inhaled glucocorticoids in conjunction with beta-2-mimetics, a considerable fraction of patients with COPD would not be administered glucocorticoids.
“Therefore, it cannot be excluded that a more severe course of asthma and COPD in patients with [the] Arg/Arg genotype of [the] ADRB2 gene at codon 16 does not result solely from the polymorphism itself, but also from the lack of [inhaled glucocorticoids].”
The Ministry of Science and Education supported the study. No conflicts of interest were declared.