Glucocorticosteroid receptor (GCR) gene isoforms expression in bronchial asthma (BA) patients

Peculiarities of GCR function is one of mechanisms of steroid dependent asthma (SDBA). Most important isoforms are CRα and CRβ, formed due to alternative splicing of NR3C1 gene. Alternatively to CRα, CRβ is not linked to glucocorticosteroids (GCS), acting as inhibitor, which concurs with CRα for linking with hormone-responding element or coactivator. This mechanism may lead to steroid resistance (SR). The aim of study was to evaluate the role of GCR isoforms in SDBA development. Methods: 9 SDBA patients, 15 ones – with mild asthma (MBA), 7 – moderate BA and 7 healthy controls were included. In 10 MBA ones, inhaled GCS were primary administered. In this group blood samples were taken before and 2 weeks after start of treatment. In SDBA patients, having long history of inhaled and oral GCS, blood was taken once. Total RNA from peripheral blood cells was isolated using RIBO-zol-B nucleic acid extraction kit (CRIE, Russia). Level of CRα and CRβ expression was evaluated by RT-qPCR method. Results: No statistic difference between expression levels in BA and controls was found. CRα expression was higher in SDBA than in other asthmatics (243,0 vs 30,7; p=0,05). In MBA during the GCS treatment trend to CRα expression increase (from 9,3 to 94,5) and CRβ expression decrease (from 820,9 to 33,3) was revealed. Significantly increased CRα/CRβ ratio in MBA after treatment (from 0,5 to 17,7; p=0,022) was same as in SDBA (19,9). Conclusions: Level of CRβ expression, which didn9t change in SDBA, can be discussed as a marker of absence of SR. Sensitivity to GCS can be evaluated basing on initial domination of CRα expression in SDBA and increase of this indicator in MBA during the course of GCS treatment.