BACKGROUND Leukotriene C4 synthase (LTC4S) gene -444A/C polymorphism has been implicated in susceptibility to asthma, but a large number of studies have reported inconclusive results. The aim of this study was to investigate the association between the -444A/C polymorphism of LTC4S gene and asthma, asthma phenotypes (aspirin intolerant/tolerant asthma) and different characteristics of the patients. METHODS We included 106 patients with asthma (60 with aspirin tolerant asthma - ATA, 46 with aspirin intolerant asthma - AIA) and 103 controls. All the subjects were genotyped for LTC4S-444 A/C by Real-Time PCR. We assessed the association of LTC4S promoter polymorphism with asthma and its phenotypes and with clinical and biological characteristics of asthmatic patients. RESULTS We did not find a significant association between the studied polymorphism and asthma, but the minor allele tended to be more frequent in AIA patients. We found a significant association between the minor allele C and lower levels of serum total immunoglobulin E and eosinophils, suggesting a possible role of -444A/C LTC4S polymorphism as modulating factor of allergic inflammation in asthma. CONCLUSIONS The results show that LTC4S -444A/C SNP is not associated with susceptibility to asthma in Romanian patients, but could influence asthma phenotype, namely aspirin intolerant asthma.