白三烯C4合成酶基因多态性与支气管哮喘患者抗白三烯治疗反应性的关系  

The relevance of leukotriene C4 synthase gene A（-444） C polymorphism to clinical responsiveness to montelukast in patients with astluna

作　　者：吴永红[1] 刘春涛[1] 王可[1] 耿艳鸣[1] 

机构地区：[1]四川大学华西医院呼吸内科,成都610041

出　　处：《中华结核和呼吸杂志》2008年第11期806-810,共5页Chinese Journal of Tuberculosis and Respiratory Diseases

摘　　要：目的探讨中国西南地区汉族支气管哮喘（简称哮喘）人群白三烯C4合成酶（LTC4S）基因多态性及其与抗白三烯治疗反应性的关系。方法选取2006年4月至2007年2月四川大学华西医院哮喘门诊的哮喘患者150例，其中男87例，女63例，平均年龄（41±14）岁；无哮喘病史健康对照146名，其中男82名，女64名，平均年龄（42±14）岁。应用聚合酶链反应-限制性片段长度多态性方法（RELP）检测LTC4SA444C基因多态性及等位基因的频率。从哮喘组中按数字随机法选取患者80例，采用白三烯受体拮抗剂孟鲁司特单药治疗4周，分别于治疗前后采用酶联免疫吸附法（ELISA）测定尿白三烯E4（LTE4）水平，根据症状积分和肺功能变化评价对抗白三烯治疗的反应性。应用多元方差分析法检测LTC4S基因-444C等位基因频率与治疗反应性的相关性。结果（1）哮喘组中LTC4S基因444位点基因型AA、AC／CC频率分别为70．7％（106／150）和29．3％（44／150），等位基因A、C频率分别为83．7％（251／300）和16．3％（49／300），健康对照组LTC4S基因444位点基因型AA、AC／CC频率分别为76．7％（112／146）和23．3％（34／146），等位基因A、C频率分别为87．0％（254／292）和13．0％（38／292），差异无统计学意义。（2）150例哮喘患者中，基因型AC／CC患者较AA型患者年轻[分别为（45±10）岁和（50±8）岁，F=5．891，P=0．037]，起病较早[分别为（38±4）岁和（46±6）岁，F=6．985，P=0．024]，病程较长[分别为（4．7±2．1）年和（3．1±2．0）年，F=11．43，P=0．013]，而其他指标两组差异无统计学意义。（3）80例哮喘患者应用孟鲁司特钠治疗4周后，基因型AC／CC患者对抗白三烯治疗的反应性优于AA型（F=12．01，P=0．011），两组患者治疗反应的差异与体内LTE4水平有关，而与肺功能指标及临床症状无关。结论西南地区汉族�Objective To investigate the frequency of leukotriene C4 synthase gene A （LTC4S A） -444 C polymorphism in asthmatics of Chinese Han nationality in Southwest China and to evaluate its relevance to clinical responsiveness to leukotriene receptor antagonist. Methods A hundred and fifty asthmatics and 146 healthy blood donors were recruited. The genotype distribution of A/C polymorphism of LTC4S A444C gene was analyzed by RELP （restriction fragment length polymorphism）. Eighty asthmatics were randomly recruited for a 4 week prospective trial of montelukast and their clinical response to montelukast was evaluated by ACQ and pulmonary function. Urine LTE4 was detected by ELISA （ enzyme linked immunosorbent assay） in asthma patients before and after treatment. Results In the 150 asthma patients , the frequencies of A and C alleles at -444. locus of LTC4S gene were 83. 7% and 16.3%, respectively, and the genotype frequencies of AA and AC/CC were 70.7% and 29.3% ,respectively. In the 146 healthy blood donors, the frequencies of A and C alleles at -444 locus of LTC4S gene were 87.0% and 13.0%, respectively, and the genotype frequencies of AA and AC/CC were 76. 7% and 23. 3%, respectively. There was no significant difference in LTC4S A-444 C polymorphism between the asthmatics and the healthy controls （ X2 = 1. 393,1.301, P = 0. 258,0. 254, P 〉 0.05 ） . The asthmatics with the C.444 allele were younger than the asthmatics with AA with earlier onset age and longer duration of disease compared to those with AA（ both P 〈 0.05 ）. However, there were no significant differences between the two groups in clinical and lung function parameters. Four-week montelukast therapeutic trial demonstrated that asthmatic patients with AC/CC genotype had better response than those with AA genotype and this difference was related to urine LTE4 level（ F = 12.01, P = 0.011 ）. Conclusion In a Southwest Chinese Han population LTC4S A444C polymorphism might be a determinant factor in the clinical response of asthma to leu

关 键 词：哮喘 白三烯C4 多态性 限制性片段长度多态性 遗传药理学 

分 类 号：R363.21[医药卫生—病理学] R562.25[医药卫生—基础医学]