Analysis of 927T > C CYSLTR1 and -444A > C LTC4S polymorphisms in children with asthma

Introduction: The cysteinyl leukotrienes (Cys-LTs) are potent inflammatory mediators in asthma. It has been suggested that the different response of patients to Cys-LTs inhibitors could be due to the presence of polymorphisms in the genes implicated in this pathway. Methods: In this study, polymorphisms 927T > C CYSLTR1 and -444A > C LTC4S were analysed in a Spanish population of 188 individuals (109 asthmatic children and 79 controls). Standardised history, skin prick tests and lung function measurements were performed in all patients. Genotypes were determined by sequencing after PCR amplification. Results: Differences were observed in 927T > C CYSLTR1, regarding the severity of asthma in males. A greater presence of allele C in the population with persistent asthma versus the control group (Fisher's p-value = 0.001; Monte Carlo p-value = 0.003; OR: 12.35; 95 %Cl: 2.18-70.00) was observed. Differences were also detected in the combined study of both polymorphisms, among controls and asthmatic patients (Monte Carlo p-value = 0.0002). In the group of males with asthma, an increase of AC variant (-444A LTC4S and 927C CYSLTR1) and a reduction in the AT genetic combination were detected. Conclusions: The combined study of polymorphisms in genes of the leukotriene pathway could explain the differences observed in the studies reported on polymorphism -444A < C LTC4S individually analysed.