5-lipoxygenase Pharmacogenetics in Asthma: Overlap with CystLTR1 Loci

摘要

The two classes of leukotriene modifiers work by inhibiting different portions of the same pathway. We hypothesized that single nucleotide polymorphisms (SNPs) in genes associated with response to montelukast (a cys-leukotriene receptor antagonist) would also be associated with response to zileuton (a 5-lipoxygenase inhibitor). We genotyped 26 SNPs that had previously been interrogated for association with montelukast response in five candidate genes (ABCC1, ALOX5, CYSLTR1, LTA4H, LTC4S) in a population of 577 asthmatics who participated in a clinical trial comparing intermittent and continuous-release zileuton to placebo. After adjusting for age and sex, six SNPs in three genes were associated with longitudinal FEV1 in response to zileuton (p-values 0.005–0.05). The SNPs included the two (ALOX5 rs2115819 and ABCC1 rs119774) that we had previously reported to be associated with FEV1 response to montelukast. Thus, the lung function response to zileuton is modulated by several of the loci that also influence montelukast response.