Leukotrienes （LTs） are synthesized from membrane derived arachidonic acid.Downstream of 5-lipoxygenase in the arachidonic acid cascade, leukotriene C4 synthase （LTC4S） catalyses the conjugation of leukotriene A4 ...Leukotrienes （LTs） are synthesized from membrane derived arachidonic acid.Downstream of 5-lipoxygenase in the arachidonic acid cascade, leukotriene C4 synthase （LTC4S） catalyses the conjugation of leukotriene A4 （LTA4） with reduced glutathione to form LTC4, then LTC4 convert to active metabolites LTD4 and LTE4. LTC4, LTD4 and LTE4, which are called cysteinyl leukotrienes （CysLTs）, are potent proinflammatory mediators of asthma. LTC4S is the key enzyme involved in the formation of CysLTs. There is a polymorphism of adenine （A） to cytosine （C） transversion at -444 locus in the promoter region of the LTC4S gene, A-444C.^1 This allelic variant results in an extra recognition site for the Ap-2 transcription factor and is associated with an increased LTC4S transcription rate.^2 Some studies in other countries suggest that LTC4S A-444C polymorphism is associated with asthmatic severity and clinical response to leukotriene receptor antagonist.^3-5 Little is known about the frequency of the LTC4S gene variant in the Chinese population. In this study, we evaluated the association of LTC4S A-444C polymorphism with susceptibility to asthma, severity of asthma and clinical response to a leukotriene receptor antagonist, montelukast, in Chinese Han people in Beijing.展开更多
文摘Leukotrienes （LTs） are synthesized from membrane derived arachidonic acid.Downstream of 5-lipoxygenase in the arachidonic acid cascade, leukotriene C4 synthase （LTC4S） catalyses the conjugation of leukotriene A4 （LTA4） with reduced glutathione to form LTC4, then LTC4 convert to active metabolites LTD4 and LTE4. LTC4, LTD4 and LTE4, which are called cysteinyl leukotrienes （CysLTs）, are potent proinflammatory mediators of asthma. LTC4S is the key enzyme involved in the formation of CysLTs. There is a polymorphism of adenine （A） to cytosine （C） transversion at -444 locus in the promoter region of the LTC4S gene, A-444C.^1 This allelic variant results in an extra recognition site for the Ap-2 transcription factor and is associated with an increased LTC4S transcription rate.^2 Some studies in other countries suggest that LTC4S A-444C polymorphism is associated with asthmatic severity and clinical response to leukotriene receptor antagonist.^3-5 Little is known about the frequency of the LTC4S gene variant in the Chinese population. In this study, we evaluated the association of LTC4S A-444C polymorphism with susceptibility to asthma, severity of asthma and clinical response to a leukotriene receptor antagonist, montelukast, in Chinese Han people in Beijing.
