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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

The relevance of leukotriene D4 synthase gene A(-444)C polymorphism to clinical responsiveness of leukotriene receptor antagonist in patients with allergic rhinitis
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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,P<0.05),起病较早(分别为31±4、46±6岁,F=6.985,P<0.05),病程较长(分别为8.7±2.1、3.1±2.0年,F=11.43,P<0.05),症状评分(8.2±0.2、4.8±0.3.t=6.95,P<0.05)、体征评分(7.3±3.3、3.4±5.1,t=8.89,P<0.05)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,P<0.05),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。 Objective:To investigate the leukotriene D4 synthase gene A(LTD4S A)-444 C polymorphism in persistent allergic rhinitis(AR) of Chinese Han nationality and to evaluate its relevance to clinical responsiveness of leukotriene receptor antagonist. Method:There were 150 patients [87 males, 63 females, average age (38±14)] diagnosed with persistent AR in Allergy clinic in our hospital from March 2010 to March 2012; 146 healthy con- trols (78 males, 68 females, mean age (39±12)). We detected LT D4SA-444C polymorphism and allele frequen- cies with Polymerase Chain Reaction(PCR) and-Restriction Fragment Length polymorphism (RELP). The treat- ment group received monotherapy leukotriene receptor antagonist (montelukast) for 4 weeks. Urinary leukotriene D4 (LTD4) levels were detected by enzyme-linked immunosorbent assay (ELISA) before and after treatment, re spectively. We evaluated anti-leukotriene treatment response according to the changement of symptoms, signs PTS and urinary LTD4. We tested correlation between LT D4S gene-444C allele frequency and the treatment re-sponse by multivariate analysis of variance. Result: O LTD4S gene-444 genotype AA/CC, AC/CC frequency is 70.7% (106/150) and 29.3% (44/150), allele A, C frequencies is 67.3% (101/150) and 32.7% (49/150) in AR group, and LTD4S gene-444 genotype AA/CC, AC/CC frequency is 76.7% (112 /146) and 23.3% (34/ 146), allele A, C frequencies is 74.0% (108/146) and 26.0% (38/146) in healthy control group, there is not statistically significant difference between two groups.Among 150 AR patients, compared to patients with AA/CC genotype, the genotype AC/CC patients are younger[average age (35±9), and (50 Jr 8) respectively, F= 5. 891, P〈0.05], with earlier age of onset [ (31±4), and (46±6) respectively, F=6. 985, P〈0.05], longer course of disease [ (8.7±2.1), and (3.1±2.0) respectively, F: 11.43, P〈0.05 ], higher symptom scores (8.2±0.2; 4.8±0.3), highe
出处 《临床耳鼻咽喉头颈外科杂志》 CAS 北大核心 2014年第14期1020-1024,共5页 Journal of Clinical Otorhinolaryngology Head And Neck Surgery
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)
关键词 鼻炎 变应性 白三烯D4 多态性 限制性片段长度 遗传药理学 rhinitis,allergic leukotriene D4 polymorphism, restriction fragment length pharmacogenetics
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