A genetic polymorphism of the LTC4S gene has been identified consisting of an A to C transversion 444 nucleotides upstream of the first codon, conferring a relative risk of AIA of 3.89.
A polymorphism study that examined nine single-nucleotide polymorphisms of five leukotriene-related genes [ALOX5 (encoding 5-lipoxygenase), ALOX5AP (5-lipoxygenase-activating protein), PTGS2 (cyclooxygenase 2), LTC4S (leukotriene C4 synthase), and CYSLTR1 (cysteinyl leukotriene receptor 1)] found that promoter polymorphisms of ALOX5 (-1708A>G) and CYSLTR1 (-634C>T) were significantly different between aspirin-intolerant asthma and aspirin-induced urticaria/angioedema, suggesting different contributions to the lipoxygenase pathway.
As previous studies have shown that cysteinyl leukotrienes are important mediators in exercise-induced bronchoconstriction (EIB), and leukotriene receptor antagonists (LTRAs) such as montelukast have been shown to improve post-exercise bronchoconstrictor responses, we herein investigated whether clinical responsiveness to montelukast was associated with polymorphisms in the genes encoding leukotriene C4 synthase (LTC4S) and cysteinyl leukotriene receptor 1 (CysLTR1) and/or clinical parameters in Korean asthmatic children with EIB.
Discovery of the Oral Leukotriene C4 Synthase Inhibitor (1<i>S</i>,2<i>S</i>)-2-({5-[(5-Chloro-2,4-difluorophenyl)(2-fluoro-2-methylpropyl)amino]-3-methoxypyrazin-2-yl}carbonyl)cyclopropanecarboxylic Acid (AZD9898) as a New Treatment for Asthma.
Improvement of asthma was observed mostly in patients with a low baseline and non-IL-5 inducible expression of LTC4 synthase (LTC4S) mRNA in eosinophils.
Lack of an association between a newly identified promoter polymorphism (-1702G > A) of the leukotriene C4 synthase gene and aspirin-intolerant asthma in a Korean population.
The LTC(4)S genotype distribution was consistent with the Hardy-Weinberg equilibrium in patients with aspirin-tolerant asthma and unaffected control subjects but not in patients with aspirin-intolerant asthma; however, the distributions were not significantly different among the phenotype groups.
The coding regions of the LTC(4) synthase gene were screened for polymorphisms and the A(-444)C polymorphism was analyzed in a large Australian white adult population of mild (n=282), moderate (n=236), and severe asthmatic subjects (n=86) and nonasthmatic subjects (n=458), as well as in aspirin-intolerant asthmatic subjects (n=67).
The density of LTC4S-positive mast cells correlated, moreover, with both the reduction in lung function and the degree of reversibility in treated asthma.
This data strongly support LTC4S as a candidate gene in this phenotype of asthma, and further characterization of LTC4S in terms of enzymatic function and gene regulation will likely contribute to the understanding of the gene as one potentially responsible for the allergic inflammation underlying aspirin-intolerance.
This meta-analysis suggested that the -444A/C polymorphism in the LTC4S gene would be a risk factor for asthma in Caucasians and aspirin-tolerant populations.