白三烯D4合成酶基因多态性与持续性变应性鼻炎患者抗白三烯治疗反应性的关系
发布时间：2018-07-26 12:49
【摘要】：目的:探讨持续性变应性鼻炎(AR)患者白三烯D4合成酶(LTD4S)基因多态性及其与抗白三烯治疗反应性的关系。方法:选取持续性AR患者150例,其中男87例,女63例,年龄(38±14)岁。健康对照者146例,其中男78例,女68例,年龄(39±12)岁。应用聚合酶链反应-限制性片段长度多态性方法(RELP)检测LTD4SA-444C基因多态性及等位基因的频率。治疗组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测定尿白三烯D4(LTD4)水平,根据症状、体征积分变化及尿LTD4水平评价抗白三烯治疗的反应性。应用多元方差分析法检测LTD4S基因-444C等位基因频率与治疗反应性的相关性。结果:①AR组中LTD4S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67.3%(101/150)和32.7%(49/150),健康对照组LTD4S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74.0%(108/146)和26.0%(38/146),差异无统计学意义。②150例AR患者中,基因型AC/CC患者较AA型患者年轻(分别为35±9、50±8岁,F=5.891,P0.05),起病较早(分别为31±4、46±6岁,F=6.985,P0.05),病程较长(分别为8.7±2.1、3.1±2.0年,F=11.43,P0.05),症状评分(8.2±0.2、4.8±0.3.t=6.95,P0.05)、体征评分(7.3±3.3、3.4±5.1,t=8.89,P0.05)更高,2组差异有统计学意义。③150例AR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=11.01,P0.05),2组患者治疗反应的差异与体内LTD4水平有关,与临床症状、体征相关。结论:襄阳地区汉族人群中LTD4SA-444C基因多态性可能与持续性AR患者应用白三烯受体拮抗剂的临床反应性相关。
[Abstract]:Aim: to investigate the relationship between leukotriene D 4 synthase (LTD4S) gene polymorphism and anti leukotriene therapeutic reactivity in patients with persistent allergic rhinitis (AR). Methods: 150 patients with persistent AR were selected, including 87 males and 63 females, aged (38 卤14) years. 146 healthy controls, including 78 males and 68 females, aged (39 卤12) years. Polymerase chain reaction-restriction fragment length polymorphism (RELP) was used to detect the frequency of LTD4SA-444C gene polymorphism and allele. The treatment group was treated with montelukast, a leukotriene receptor antagonist, for 4 weeks. The levels of urinary leukotriene D _ 4 (LTD4) were measured by enzyme-linked immunosorbent assay before and after treatment. To evaluate the reactivity of anti-leukotriene therapy with the changes of sign score and urinary LTD4 level. Multivariate variance analysis was used to detect the correlation between the allele frequency of LTD4S gene -444C and the therapeutic reactivity. Results in the 1: 1AR group, the frequencies of LTD4S gene -444 locus genotype AAC / CC were 70.7% (106 / 150) and 29.3% (44 / 150), respectively, and the alleles were 67.3% (101 / 150) and 32.7% (49 / 150), respectively. In the healthy control group, the frequencies of LTD4S -444 locus genotype AAAAC / CC were 76.7% (112 / 146) and 23.3% (34 / 146), respectively, and the frequencies of the alleles were 67.3% (101 / 150) and 32.7% (49 / 150), respectively. The difference was 74.0% (108 / 146) and 26.0% (38 / 146), and there was no significant difference among 2150 AR patients. The patients with genotype AC/CC were younger than those with AA type (35 卤9 卤50 卤8 years old, P 0.05), the onset of disease was earlier (31 卤4 46 卤6 years old), the course of disease was longer (8.7 卤2.1 卤3.1 卤2.0 years), the symptom score was (8.2 卤0.24.8 卤0.3tl 卤6.95 P 0.05), the physical sign score (7.3 卤3.3 卤5.1tl) was higher than that of the two groups (P < 0.05). There was significant difference between the two groups. Patients were treated with montelukast sodium for 4 weeks. The response to leukotriene therapy in genotype AC/CC patients was better than that in AA group (FV 11.01P 0.05). The difference of therapeutic response was related to the level of LTD4 in the body, and was related to clinical symptoms and signs. Conclusion: the polymorphism of LTD4SA-444C gene in Xiangyang Han population may be related to the clinical reactivity of leukotriene receptor antagonists in patients with persistent AR.
【作者单位】： 湖北文理学院附属医院;襄阳市中心医院药学部;襄阳市中心医院耳鼻咽喉科;襄阳市中心医院检验科;
【基金】：科技部十一五科技支撑计划子课题(No:2007BAI18B15) 湖北省自然科学基金(No:2011CDB320) 湖北省卫生厅项目(No:JX5C26)
【分类号】：R765.21
[Abstract]:Aim: to investigate the relationship between leukotriene D 4 synthase (LTD4S) gene polymorphism and anti leukotriene therapeutic reactivity in patients with persistent allergic rhinitis (AR). Methods: 150 patients with persistent AR were selected, including 87 males and 63 females, aged (38 卤14) years. 146 healthy controls, including 78 males and 68 females, aged (39 卤12) years. Polymerase chain reaction-restriction fragment length polymorphism (RELP) was used to detect the frequency of LTD4SA-444C gene polymorphism and allele. The treatment group was treated with montelukast, a leukotriene receptor antagonist, for 4 weeks. The levels of urinary leukotriene D _ 4 (LTD4) were measured by enzyme-linked immunosorbent assay before and after treatment. To evaluate the reactivity of anti-leukotriene therapy with the changes of sign score and urinary LTD4 level. Multivariate variance analysis was used to detect the correlation between the allele frequency of LTD4S gene -444C and the therapeutic reactivity. Results in the 1: 1AR group, the frequencies of LTD4S gene -444 locus genotype AAC / CC were 70.7% (106 / 150) and 29.3% (44 / 150), respectively, and the alleles were 67.3% (101 / 150) and 32.7% (49 / 150), respectively. In the healthy control group, the frequencies of LTD4S -444 locus genotype AAAAC / CC were 76.7% (112 / 146) and 23.3% (34 / 146), respectively, and the frequencies of the alleles were 67.3% (101 / 150) and 32.7% (49 / 150), respectively. The difference was 74.0% (108 / 146) and 26.0% (38 / 146), and there was no significant difference among 2150 AR patients. The patients with genotype AC/CC were younger than those with AA type (35 卤9 卤50 卤8 years old, P 0.05), the onset of disease was earlier (31 卤4 46 卤6 years old), the course of disease was longer (8.7 卤2.1 卤3.1 卤2.0 years), the symptom score was (8.2 卤0.24.8 卤0.3tl 卤6.95 P 0.05), the physical sign score (7.3 卤3.3 卤5.1tl) was higher than that of the two groups (P < 0.05). There was significant difference between the two groups. Patients were treated with montelukast sodium for 4 weeks. The response to leukotriene therapy in genotype AC/CC patients was better than that in AA group (FV 11.01P 0.05). The difference of therapeutic response was related to the level of LTD4 in the body, and was related to clinical symptoms and signs. Conclusion: the polymorphism of LTD4SA-444C gene in Xiangyang Han population may be related to the clinical reactivity of leukotriene receptor antagonists in patients with persistent AR.
【作者单位】： 湖北文理学院附属医院;襄阳市中心医院药学部;襄阳市中心医院耳鼻咽喉科;襄阳市中心医院检验科;
【基金】：科技部十一五科技支撑计划子课题(No:2007BAI18B15) 湖北省自然科学基金(No:2011CDB320) 湖北省卫生厅项目(No:JX5C26)
【分类号】：R765.21
【参考文献】
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1 刘晓玲;罗鸿;张建斌;严能兵;付选香;沈莹;余晔;刘s，
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