Objectives To investigate the frequency of LTC4S A-444C polymorphism in Chinese Han population in Beijing and to evaluate its association with susceptibility to asthma,asthma severity and clinical response to leukotriene receptor antagonist.Methods The LTC4S A-444C polymorphism was analyzed in 101 patients with asthma and 105 healthy controls.Then 18 asthmatics were recruited,and a 2-week prospective,open trial of montelukast was performed in addition to the previous medications.Results In the asthma group,the frequencies of A and C allele at -444 locus of LTC4S gene were 81.0% and 19.0%,respectively,and genotype frequencies of AA,AC and CC were 65.4%,30.5% and 3.8%,respectively.There was no significant difference in LTC4S A-444C polymorphism between the asthmatics and healthy controls(Pgt;0.05).The asthmatics with the C-444 allele had significantly lower forced expiratory volume in one second(FEV1) than wild-type A homozygotes [(58.6±21.6)% predicted vs (70.3±22.4)% predicted,Plt;0.05)].A correlation was observed between the variant C-444 allele and asthma severity(Plt;0.05).After administered montelukast 1 week,the A-444 allele homozygotes(n=9) responded better than the C(-444) allele carriers(n=7)[(10.8±10.2)% vs (–9.8±16.2)% improvement of FEV1,Plt;0.05].After 2 weeks,the A-444 allele hemozygotes also responded better,although there was no statistical difference(Pgt;0.05).Conclusion In Chinese Han population LTC4S A-444C polymorphism is associated with asthma severity and probably contributes to the clinical response to leukotriene receptor antagonists.