The role of histone deacetylase 2 (HDAC2) and glucocorticoid receptor (GR) isoformsα,βin patients with asthma–COPD overlap syndrome (ACOS)

Background. HDAC2 and GRα , β define steroid sensitivity (SS), but their roles are poorly understood in ACOS. Aim: To estimate the expression of HDAC2 and GR α , β in patients with ACOS. Methods: We examined 31 exacerbated ACOS patients (aged 63,7±9,83 years) and 32 controls. Relative mRNA quantification of HDAC2 and GR α , β was performed by real-time PCR (TaqMan Chemisty). Results: In patients with ACOS, the number of exacerbations ≥2 was associated with higher dose of intravenous glucocorticoid therapy (ivGT)(r=0,409;p=0,025), with ivGT duration (r=0,475;p=0,008), and with blood erythrocytosis (BE)(r=0,373;p=0,042). In ACOS, HDAC2 gene expression was lower (1,17 ± 0,34) than in controls (1,43 ± 0,43)(p=0,008), and correlated with BE (r=-0,381;p=0,035). Patients with ESR≥15 mm/h had higher levels of HDAC2 [1,51(1,06;2,04)], than patients with normal ESR [1,11(0,72;1,37)] (p=0,019). In ACOS, GRα mRNA levels correlated with GRβ (r=0,634;p=0,0001), and with GRα/β ratio (r=0,401;p=0,026). The number of hospitalizations correlated with the mRNA levels of both GRα (r=0,582;p=0,001) and GRβ (r=0,391;p=0,03). The increase in mRNA GRα (r=0,498;p=0,004) correlated with increase in HDAC2 expression. The increase in mRNA GRβ was associated with the increase in RV (r=0,359;p=0,047), RV/TLC% (r=0,567;p=0,011) and decrease in Sgaw (r=-0,459;p=0,042). The decrease in mRNA GRα / mRNA GRβ ratio correlated with increase in ivGT dose (r=-0,364;p=0,044) and BE (r=-0,365;p=0,044). Conclusions: Decreased in HDAC2 and GRα mRNA levels, and increased GRβ mRNA levels may be considered as markers of decreased SS in patients with ACOS.