Association analysis of the glucocorticoid receptor gene (NR3C1) haplotypes (ER22/23EK, N363S, BclI) with mood and anxiety disorders in patients with asthma

Chronic inflammation in the bronchi of long-term asthma patients worsens mood disorders, which has been shown to correlate with elevated levels of multiple proinflammatory cytokines. The glucocorticoid receptor (GR) gene, NR3C1, plays a key role in the control of inflammation. Disturbances in the structure and function of the GR alter the glucocorticoid regulation of the corticotropin-releasing hormone, which leads to nonspecific activation of numerous receptors in the brain and alters the metabolism. The aim of the present study was to evaluate the role of NR3C1 haplotypes in mood and anxiety disorders. The study included 235 patients with asthma and 216 healthy individuals. Genotyping of NR3C1 gene polymorphisms was performed using polymerase chain reaction-restriction fragment length polymorphism. Beck's Depression Inventory, State and Trait Anxiety Inventory tests and the Borg scale were applied for all the subjects. Significant differences in the levels of depression (P=0.000008) and dyspnea (P=0.000001) were observed between the patients and healthy subjects. In addition, a correlation was identified between spirometric parameters and the intensity of depression, anxiety and subjective dyspnea. The AA ER22/23EK, AA N363S and CC BclI haplotype of the NR3C1 gene was identified to significantly aggravate trait anxiety in patients with asthma (P=0.026). Therefore, the NR3C1 gene substantially modified the level of trait anxiety in asthma sufferers.