We studied 61 patients with asthma and/or atopy and 129 to 157 newborn controls for the -403 RANTES, -28 RANTES, and -1055 IL-13 SNPs, as well as 47 patients and 60 newborn controls for the -444 LTC4S SNP.
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.
We conclude that LTC(4) S genotype is predictive of the clinical response to a cysLT(1) antagonist, pranlukast, in Japanese patients with moderate asthma.
We conclude that LTC(4) S genotype is predictive of the clinical response to a cysLT(1) antagonist, pranlukast, in Japanese patients with moderate asthma.
We analyzed the effects of LTC4S-444 A/C, ALOX5 -176/-147, and ALOX5AP -169/-146 on asthma susceptibility by means of a case-control study with 193 ethnically matched, unrelated individuals.
Two RANTES -403(G to A) and -28(C to G), an -1055 IL-13(C to T), and a -444(A to C) leukotriene C4 synthase (LTC4S) single nucleotide polymorphisms (SNPs) have been shown in Caucasians and Asians as asthma and atopy risk factors.
Those specific variants include 2 variants in the 5-lipoxygenase gene (ALOX5) that are both associated with response to 5-lipoxygenase inhibition and to leukotriene receptor antagonists, variants in genes encoding the 2 established cysteinyl leukotriene receptor antagonists (CYSLTR1 and CYSLTR2) that are both associated with asthma susceptibility in at least 2 independent populations, and a leukotriene C(4) synthase promoter polymorphism (LTC4s) that has been associated with asthma affection status and asthma-exacerbated respiratory disease.
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.
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.
The density of LTC4S-positive mast cells correlated, moreover, with both the reduction in lung function and the degree of reversibility in treated asthma.
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 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.
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.
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.
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.