查看文章

Objective

Interindividual clinical response to leukotriene modifiers is highly variable, and less efficacious than inhaled corticosteroids in treating asthma. Genetic variability in 5-lipoxygenase biosynthetic and receptor pathway gene loci may influence cysteinyl-leukotriene production and subsequent response to leukotriene modifiers.

Methods

Using data from two clinical trials of 12-week duration, post-hoc analyses were performed in 174 patients randomized to montelukast. Associations between polymorphisms in 10 candidate genes (ALOX5, ALOX5AP, LTC4S, CYSLTR1, CYSLTR2, PLA2G4A, CYP2C9, CYP3A4, ADRB2, and NR3C1) and response to montelukast were modeled using change in morning peak expiratory flow and forced expiratory volume in 1 s (FEV 1) to define the response phenotype.

Results

In our sample, eight out of 25 markers in 10 candidate genes were statistically associated with response to …