Introduction: Resistance to corticosteroid is an essential mechanism in uncontrolled asthma
as the corticosteroid is the mainstay of therapy. There are recent reports that epigenetic factors play a
crucial role in the regulation of steroid action. Overexpression of P glycoprotein (P-gp) and reduced
expression of Histone Deacetylase 2 (HDAC2) have been linked to regulating the steroid action in other
diseases like Nephrotic Syndrome (NS). However, their role in uncontrolled asthma is still not clear
and warrants further investigation. We evaluated the expression and activity of P-gp and HDAC2 in
patients with Controlled Asthma (CA) and Uncontrolled Asthma (UA).
Methods: A total of 60 CA (mean age 51.72±17.02 years, male=38), and 38 of UA (mean
age=53.55±11.90 years, male=17) were recruited. The level of control was defined according to
(Global Initiative for Asthma) GINA 2016 criteria. The mRNA expression of HDAC2 and P-gp was
studied by quantitative real-time Polymerase Chain Reaction (PCR), the functional activity of P-gp
was evaluated by a commercially available kit via flow cytometry, and HDAC2 enzymatic activity was
measured by commercially available kit by Enzyme-Linked Immunosorbent Assay (ELISA).
Results: P-gp expression and the functionality were significantly higher in the UA group of patients as
compared to the CA group of patients (p<0.005), moreover HDAC2 expression was significantly reduced
in UA patients as compared to CA patients, (p<0.005). The enzymatic activity of HDAC2 was also significantly
reduced in UA patients as compared to CA patients (p<0.005).
Conclusion: P-gp overexpression and HDAC2 under expression play an essential role in uncontrolled
asthma by impairing the response to corticosteroid.