大豆异黄酮通过产生高表达PAI-1的基因型减少哮喘患者的哮喘急性发作
2019/02/19
摘要
背景：纤溶酶原激活物抑制剂-1（PAI-1）的4G4G基因型与血浆PAI-1水平升高和哮喘控制不良有关。既往研究表明，大豆异黄酮可能会降低PAI-1水平。
目标：我们试图调查哮喘患者中大豆异黄酮反应的PAI-1基因型特异性差异。
方法：PAI-1功能多态性（rs1799768,4G5G）在接受大豆异黄酮随机临床试验（n = 265）的哮喘控制不佳的受试者中进行了表征。比较大豆异黄酮与安慰剂对哮喘结局的基因型特异性治疗反应。 在有或没有TGF-β1和/或染料木黄酮的情况下培养正常人支气管上皮细胞（NHBE），并测量PAI-1水平。
结果：与5G5G基因型相比，4G4G / 4G5G基因型与过敏相关的哮喘症状和湿疹的风险增加相关。 基因型和大豆异黄酮干预用于哮喘急性发作的口服皮质类固醇之间存在显着的相互作用（p = 0.005）。在亚组分析中，与4G4G / 4G5G基因型中的安慰剂相比，大豆异黄酮显着降低口服皮质类固醇的使用（事件数/人年）4倍（0.2 vs 0.8，相对风险0.28，p <0.001） 但并没有发生在5G5G基因型中。与安慰剂相比，大豆异黄酮降低血浆PAI-1水平。经过Genistein处理降低NHBE中TGF-β1诱导的PAI-1产生。
结论：该研究表明，大豆异黄酮在减少哮喘患者中具有高PAI-1产生基因型的重症哮喘急性发作的次数方面具有显著益处。PAI-1多态性可用作哮喘患者应用大豆异黄酮的遗传学层面的生物标志物。
（中日友好医院呼吸与危重症医学科 张鑫 摘译 林江涛 审校）
（J Allergy Clin Immunol. 2019 Jan 29. doi: 10.1016/j.jaci.2019.01.020.）
（J Allergy Clin Immunol. 2019 Jan 29. doi: 10.1016/j.jaci.2019.01.020.）
Soy isoflavones reduce asthma exacerbation in asthmatics with high PAI-1 producing genotypes.
Cho SH, Jo AR
Abstract
BACKGROUND: The 4G4G genotype of plasminogen activator inhibitor-1 (PAI-1) is associated with increased plasma PAI-1 levels and poor asthma control. Previous studies suggest that soy isoflavones may reduce PAI-1 levels.
OBJECTIVE: We sought to investigate PAI-1 genotype-specific differences of the soy isoflavone response in asthma outcomes.
METHODS: A PAI-1 functional polymorphism (rs1799768, 4G5G) was characterized in subjects with poorly controlled asthma enrolled in a randomized clinical trial of soy isoflavones (n=265). Genotype-specific treatment responses on asthma outcomes were compared between soy isoflavones versus placebo. Normal human bronchial epithelial cells (NHBE) were cultured with or without TGF-β1 and/or genistein, and PAI-1 levels were measured.
RESULTS: The 4G4G/4G5G genotype was associated with a higher risk for allergy-related worsened asthma symptoms and eczema at baseline compared to the 5G5G genotype. There was a significant interaction between the genotype and soy isoflavone intervention on oral corticosteroid use for asthma exacerbation (p=0.005). In a subgroup analysis, soy isoflavones significantly reduced the use of oral corticosteroids (number of events/person-year) by four-fold compared to the placebo in the 4G4G/4G5G genotype (0.2 vs 0.8, relative risk 0.28, p <0.001) but not in the 5G5G genotype. Soy isoflavones reduced plasma PAI-1 levels compared to the placebo. Genistein treatment reduced TGF-β1-induced PAI-1 production in NHBE.
CONCLUSIONS: This study demonstrates that soy isoflavone treatment provides a significant benefit in reducing the number of severe asthma exacerbations in asthmatic subjects with the high PAI-1 producing genotype. PAI-1 polymorphisms can be used as a genetic biomarker for soy isoflavone responsive subjects with asthma.
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有氧运动对哮喘分子方面的影响：SOCS-JAK-STAT的参与
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AMP及腺苷导致的呼吸困难与哮喘患者大小气道功能障碍的关系
