Arginase 1 and arginase 2 variations associate with asthma, asthma severity and β2 agonist and steroid response
Arginase 1 and arginase 2 variations associate with asthma, asthma severity and β2 agonist and steroid response
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DOI：
10.1097/fpc.0b013e328336c7fd
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发表时间：
2010-03-01
影响因子：
2.6
通讯作者：
Meurs, Herman
中科院分区：
文献类型：
--
作者：
Vonk, Judith M.;Postma, Dirkje S.;Meurs, Herman
精氨酸酶可能在哮喘的发生、严重程度和进展中起重要作用。目的研究哮喘β受体激动剂对FEV 1的逆转作用，探讨哮喘β受体激动剂对FEV 1的逆转作用，以及哮喘β受体激动剂对FEV 1的逆转作用，探讨哮喘β受体激动剂对FEV 1的逆转作用。方法对1962-1975年的200例哮喘患者进行了研究，并在1990- 1999年进行了复查。1999年，与家人团聚。从医疗记录中提取肺功能和治疗的纵向数据。单倍型标记的多态性之间的关联，α-淀粉酶1（n=3）和α-淀粉酶2（n=8）和哮喘，哮喘的严重程度，急性反应支气管扩张剂和慢性反应吸入皮质类固醇进行了analysed. Measures和主要结果α-淀粉酶2（rs 17249437和rs3742879）的两个多态性与哮喘和更严重的气道阻塞。气道高反应性增加和β 2受体激动剂可逆性降低，但与抗胆碱能可逆性无关，与β 2受体激动剂1和β 2受体激动剂2均相关。吸入性糖皮质激素可减缓FEV 1的年下降，但在β 2受体激动剂rs 2781667纯合子携带者中效果明显较差。结论β 2受体激动剂与儿童哮喘的相关性在成人哮喘中同样存在，但其可逆性较低。此外，我们还发现，哮喘患者的肺功能较低，气道高反应性较重，对吸入性皮质类固醇的长期反应较低，这反映了哮喘患者的哮喘严重程度与呼吸酶1和呼吸酶2基因相关。对多态性功能的研究是必要的，以进一步揭示这些观察结果背后的复杂机制。药理遗传学和基因组学20：179-186（C）2010年威科健康垂直栏Lippincott威廉姆斯&威尔金斯。
Rationale Arginase probably plays an important role in asthma development, severity and progression. Polymorphisms in arginase 1 and arginase 2 genes have been associated with childhood asthma and FEV1 reversibility to beta(2) agonists.Objectives We investigated the association between arginase 1 and arginase 2 polymorphisms and adult asthma, asthma severity and treatment response in a longitudinal cohort of 200 asthma patients.Methods Patients were studied during 1962-1975 and reexamined during 1990-1999, together with their families. Longitudinal data on lung function and treatment were extracted from medical records. Associations between haplotype-tagging polymorphisms in arginase 1 (n=3) and arginase 2 (n=8) and asthma, asthma severity, acute response to bronchodilators and chronic response to inhaled corticosteroids were analyzed.Measurements and main results Two polymorphisms in arginase 2 (rs17249437 and rs3742879) were associated with asthma and with more severe airway obstruction. Increased airway hyperresponsiveness and lower beta(2) agonist reversibility, but not anticholinergic reversibility, were associated with both arginase 1 and arginase 2. Inhaled corticosteroids slowed down the annual FEV1 decline, which was significantly less effective in homozygote carriers of the C-allele of the arginase 1 polymorphism, rs2781667.Conclusion We show that previously reported associations between arginase polymorphisms and childhood asthma are also present in adult asthma and the previously found associations with lower reversibility are specific for beta(2) agonists. Furthermore, we identified associations of arginase 1 and arginase 2 genes with asthma severity, as reflected by a lower lung function, more severe airway hyperresponsiveness, and less long-term response to inhaled corticosteroids. Studies on the functionality of the polymorphisms are warranted to further unravel the complex mechanisms underlying these observations. Pharmacogenetics and Genomics 20:179-186 (C) 2010 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins.