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.