Pharmacogenetic study of the effects of NK2R G231E G>A and TBX21 H33Q C>G polymorphisms on asthma control with inhaled corticosteroid treatment.

BACKGROUND AND OBJECTIVE Inhaled corticosteroids (ICS) are widely used as maintenance regimens for asthma patients. However, response to ICS shows marked inter-individual variability. Genetic factors have been shown to be potential predictors of responsiveness to ICS. We aimed to evaluate those pharmacogenetic effects on asthma control in further detail. METHODS Fifty-three mild-to-moderate asthmatics were genotyped for four genetic polymorphisms of four genes: beta2-adrenergic receptor (ADRB2), adenylate cyclase 9 (ADCY9), neurokinin receptor 2 (NK2R) and T-box 21 (TBX21). The principal clinical outcome was the achievement of asthma control, as assessed using the Global Initiative for Asthma (GINA) guidelines. During treatment with ICS, the forced expiratory volume in 1 second (FEV(1)), maximal mid-expiratory flow (MMEF) and peak expiratory flow rate (PEFR) were monitored every 4 weeks and twice daily. RESULTS Forty-eight of the 53 patients with asthma were in a controlled or partly controlled state after 12 weeks of treatment with ICS, whereas five asthmatics were in an uncontrolled state even after active treatment. Of the four genetic polymorphisms examined, NK2R G231E G>A and TBX21 H33Q C>G were significantly associated with asthma control status (P = 0.041 and P = 0.006). The subjects with wild-type alleles at each polymorphism showed a significant association with the well-controlled or partly controlled state, as compared to those with mutant alleles. At 5-12 weeks after ICS treatment, the NK2R G231E G>A was associated with therapeutic response to ICS, as reflected by improvement in predicted FEV(1)%. CONCLUSION Our results suggest that NK2R G231E G>A and TBX21 H33Q C>G are genetic predictors of response to ICS, at least with respect to asthma control status and changes in FEV(1)%, in Korean patients with asthma. Further prospective validation of those associations is necessary.