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Pharmacogenetics of asthma controller treatment.

ABSTRACT: The interpatient variability in response to asthma controllers is significant and associates with pharmacogenomic variability. The goal of the present study was to identify novel variants that associate with response to common asthma controllers: fluticasone, combination of fluticasone + salmeterol and montelukast with single nucleotide polymorphisms (SNPs) in ?2-adrenergic receptor, corticosteroid and leukotriene pathway candidate genes. Participants in a large clinical trial of step-down strategies volunteered for this pharmacogenetic study. A total of 169 SNPs in 26 candidate genes were genotyped in 189 Caucasian participants with asthma who took either fluticasone (100??g bid), fluticasone propionate (100??g) + salmeterol (50??g) (FP/Salm) or montelukast (5 or 10?mg) each night for 16 weeks. Primary outcomes were the slopes of plots of Asthma Control Questionnaire (ACQ) scores versus time following randomization; and the percent change in percent predicted FEV1 (?FEV1%pred) from enrollment to the end of the study. Associations between SNPs and outcomes were analyzed using general linear models. False discovery rate and Bonferroni corrections were used to correct for multiple comparisons. In all, 16 SNPs in seven genes were significantly associated with outcomes. For FP/Salm, three SNPs in CHRM2 associated with ACQ slope (P=2.8 × 10??), and rs1461496 in HSPA8 associated with ?FEV1%pred. For fluticasone, five SNPs in CRHR1 (P=1.9 × 10??), and three SNPs in COL2A1 associated with ACQ slope and ?FEV1%pred, respectively. For montelukast, four SNPs in CHRM2 associated with ?FEV1%pred and predicted an opposite effect compared with fluticasone (P=9 × 10?³). The present study indentified several novel SNPs that associate with response to common asthma controllers, and support further pharmacogenomic study and the use of genetic variants to personalize asthma treatment.

SUBMITTER: Mougey EB

PROVIDER: S-EPMC5875925 | biostudies-literature | 2013 Jun

REPOSITORIES: biostudies-literature

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Pharmacogenetics of asthma controller treatment.

Mougey E B EB Chen C C Tantisira K G KG Blake K V KV Peters S P SP Wise R A RA Weiss S T ST Lima J J JJ

The pharmacogenomics journal 20120228 3

The interpatient variability in response to asthma controllers is significant and associates with pharmacogenomic variability. The goal of the present study was to identify novel variants that associate with response to common asthma controllers: fluticasone, combination of fluticasone + salmeterol and montelukast with single nucleotide polymorphisms (SNPs) in β2-adrenergic receptor, corticosteroid and leukotriene pathway candidate genes. Participants in a large clinical trial of step-down strat ...[more]

PMID: 22370858

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Project description:Despite previous findings of therapeutic effects for heart rate variability biofeedback (HRVB) on asthma, it is not known whether HRVB can substitute either for controller or rescue medication, or whether it affects airway inflammation. Sixty-eight paid volunteer steroid naïve study participants with mild or moderate asthma were given 3 months of HRVB or a comparison condition consisting of EEG alpha biofeedback with relaxing music and relaxed paced breathing (EEG+), in a two-center trial. All participants received a month of intensive asthma education prior to randomization. Both treatment conditions produced similar significant improvements on the methacholine challenge test (MCT), asthma symptoms, and asthma quality of life (AQOL). MCT effects were of similar size to those of enhanced placebo procedures reported elsewhere, and were 65% of those of a course of a high-potency inhaled steroid budesonide given to a sub-group of participants following biofeedback training. Exhaled nitric oxide decreased significantly only in the HRVB group, 81% of the budesonide effect, but with no significant differences between groups. Participants reported becoming more relaxed during practice of both techniques. Administration of albuterol after biofeedback sessions produced a large improvement in pulmonary function test results, indicating that neither treatment normalized pulmonary function as a potent controller medication would have done. Impulse oscillometry showed increased upper airway (vocal cord) resistance during biofeedback periods in both groups. These data suggest that HRVB should not be considered an alternative to asthma controller medications (e.g., inhaled steroids), although both biofeedback conditions produced some beneficial effects, warranting further research, and suggesting potential complementary effects. Various hypotheses are presented to explain why HRVB effects on asthma appeared smaller in this study than in earlier studies. Clinical Trial Registration NCT02766374.

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Pharmacogenetics of asthma controller treatment.

Publications

Pharmacogenetics of asthma controller treatment.

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