G894T polymorphism of eNOS gene is a predictor of response to combination of inhaled corticosteroids with long-lasting β2-agonists in asthmatic children
G894T polymorphism of eNOS gene is a predictor of response to combination of inhaled corticosteroids with long-lasting β2-agonists in asthmatic children
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DOI：
10.2217/pgs.12.120
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发表时间：
2012-09-01
期刊：
影响因子：
2.1
通讯作者：
Manolopoulos, Vangelis G.
中科院分区：
文献类型：
--
作者：
Iordanidou, Maria;Paraskakis, Emmanouil;Manolopoulos, Vangelis G.
目的：一氧化氮合酶在哮喘患儿气道炎症中起重要作用。在本研究中，eNOS基因多态性与吸入皮质类固醇（ICS）和长效β（2）-激动剂（LABA）的反应之间的关联进行了调查。患者和方法：采用PCR-RFLP方法对81例哮喘患儿和96例健康对照者进行eNOS G894 T和-786T/C多态性及其单倍型的基因分型。结果：G894 T和-786T/C多态性与哮喘易感性无关。在哮喘儿童中，894例TT携带者对ICS加LABA的1秒用力呼气量（FEV 1）变化高于894例GG携带者（21.9 +/- 3.8 vs 1.6 +/- 1.9%; p < 0.001）。在有反应者（FEV 1变化>= 7.5%）中，894 TT基因型的频率显着高于无反应者（26.2% vs 2.6%，p < 0.001）。单独的-786T/C多态性的结果不太清楚，在大多数情况下不显着。结论：G894 T多态性与ICS的反应相关，可能是哮喘儿童ICS加LABA反应的一个有用的药物遗传学标志物。
Aim: Nitric oxide synthase enzymes have an important role in airway inflammation in asthmatic children. In the present study, the association between eNOS gene polymorphisms and response to inhaled corticosteroids (ICS) and long-lasting beta(2)-agonists (LABAs) was investigated. Patients & methods: A total of 81 asthmatic children treated with ICS plus LABAs and 96 healthy controls were genotyped for eNOS G894T and -786T/C polymorphisms and their haplotypes using the PCR-RFLP method. Results: G894T and -786T/C polymorphisms were not associated with asthma susceptibility. Among asthmatic children, 894TT carriers had higher change in forced expiratory volume in 1 s (FEV1) in response to ICS plus LABAs compared with 894GG carriers (21.9 +/- 3.8 vs 1.6 +/- 1.9%; p < 0.001). In responders (FEV1 change >= 7.5%), frequency of 894TT genotype was significantly higher than in nonresponders (26.2 vs 2.6%, p < 0.001). Results for the -786T/C polymorphism alone were less clear and in most cases nonsignificant. Conclusion: The G894T polymorphism was associated with response to ICS and may serve as a useful pharmacogenetic marker of response to ICS plus LABAs in asthmatic children.