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.
BACKGROUND AND OBJECTIVE: Inhaled corticosteroids (ICS) are widely used as maintenance regimens for asthmapatients. 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, NK2RG231E G>A and TBX21H33Q 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 NK2RG231E G>A was associated with therapeutic response to ICS, as reflected by improvement in predicted FEV(1)%. CONCLUSION: Our results suggest that NK2RG231E G>A and TBX21H33Q 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.
Authors: Huong Duong-Thi-Ly; Ha Nguyen-Thi-Thu; Long Nguyen-Hoang; Hanh Nguyen-Thi-Bich; Timothy J Craig; Sy Duong-Quy Journal: J Int Med Res Date: 2017-01-25 Impact factor: 1.671
Authors: Jesús Miguel García-Menaya; Concepción Cordobés-Durán; Elena García-Martín; José A G Agúndez Journal: Front Pharmacol Date: 2019-05-21 Impact factor: 5.810
Authors: Amber Dahlin; Joshua Denny; Dan M Roden; Murray H Brilliant; Christie Ingram; Terrie E Kitchner; James G Linneman; Christian M Shaffer; Peter Weeke; Hua Xu; Michiaki Kubo; Mayumi Tamari; George L Clemmer; John Ziniti; Michael J McGeachie; Kelan G Tantisira; Scott T Weiss; Ann Chen Wu Journal: Immun Inflamm Dis Date: 2015-07-14