一个PAI-1基因多态性与哮喘生命早期感染的风险、加重，和降低肺功能的关系
2016/10/09
摘要
背景：纤溶酶原激活物抑制剂-1（PAI-1）是由病毒在呼吸道诱发并且可能参与哮喘气道重塑。我们试图评估是否遗传变异和早期生命的下呼吸道感染能共同影响哮喘风险。
方法：我们从美国5个中心和波多黎各，排除不完整的临床和遗传数据的受试者后，招募了年龄8-21岁的拉丁裔儿童，青少年和年轻的成年人（1736名医生诊断为哮喘的患者和1747名健康对照受试者）。我们评估了在哮喘风险、哮喘加重、和肺功能的头2年内， PAI-1获得的功能多态性和毛细支气管炎/呼吸道合胞病毒（RSV）或其它的下呼吸道感染（LRI）的独立影响和联合作用。
结果：呼吸道合胞病毒感染（RSV）（OR 9.9，95% CI 4.9-20.2）和其它的下呼吸道感染(LRI)（OR 9.1，95% CI 7.2-11.5）分别与哮喘独立相关，但PAI-1基因型与哮喘不独立相关。基因型-RSV（OR 17.7，95% CI 6.3-50.2）和基因型-LRI（OR 11.7，95% CI 8.8-16.4）对哮喘风险有联合作用。基因型-RSV的联合作用导致复发哮喘住院的风险增加了3.1倍。在基因型与呼吸道感染共同作用分析中，预测的FEV1%和FEV1/FVC %在基因型-LRI组进一步降低（β-2.1，95% CI -4.0 到-0.2；β – 2.0，95% CI -3.1 到- 0.8）。同样地，在基因型-RSV组观察到低的FEV1%预计值（β-3.1，95% CI -6.1至-0.2）与低的FEV1/FVC %预测趋势。
结论：在这个拉丁美洲人群中，PAI-1的遗传变异与早期LRI如RSV毛细支气管炎与哮喘的风险增加、发病率、和降低肺功能相关。
（杨冬 审校）
PLoS One. 2016 Aug 24;11(8):e0157848. doi: 10.1371/journal.pone.0157848. eCollection 2016.
Association of a PAI-1 Gene Polymorphism and Early Life Infections with Asthma Risk, Exacerbations, and Reduced Lung Function.
Cho SH1,2, Min JY3, Kim DY1, Oh SS4, Torgerson DR4, Pino-Yanes M4, Hu D4, Sen S5, Huntsman S4, Eng C4, Farber HJ6, Rodriguez-Cintron W7,Rodriguez-Santana JR8, Serebrisky D9, Thyne SM10, Borrell LN11, Williams LK12,13, DuPont W14, Seibold MA15, Burchard EG4, Avila PC1, Kumar R16,17.
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Abstract
BACKGROUND:Plasminogen activator inhibitor-1 (PAI-1) is induced in airways by virus and may mediate asthmatic airway remodeling. We sought to evaluate if genetic variants and early life lower respiratory infections jointly affect asthma risk.
METHODS:We included Latino children, adolescents, and young adults aged 8-21 years (1736 subjects with physician-diagnosed asthma and 1747 healthy controls) from five U.S. centers and Puerto Rico after excluding subjects with incomplete clinical or genetic data. We evaluated the independent and joint effects of a PAI-1 gain of function polymorphism and bronchiolitis / Respiratory Syncytial Virus (RSV) or other lower respiratory infections (LRI) within the first 2 years of life on asthma risk, asthma exacerbations and lung function.
RESULTS:RSV infection (OR 9.9, 95%CI 4.9-20.2) and other LRI (OR 9.1, 95%CI 7.2-11.5) were independently associated with asthma, but PAI-1 genotype was not. There were joint effects on asthma risk for both genotype-RSV (OR 17.7, 95% CI 6.3-50.2) and genotype-LRI (OR 11.7, 95% CI 8.8-16.4). A joint effect of genotype-RSV resulted in a 3.1-fold increased risk for recurrent asthma hospitalizations. In genotype-respiratory infection joint effect analysis, FEV1% predicted and FEV1/FVC % predicted were further reduced in the genotype-LRI group (β -2.1, 95% CI -4.0 to -0.2; β -2.0, 95% CI -3.1 to -0.8 respectively). Similarly, lower FEV1% predicted was noted in genotype-RSV group (β -3.1, 95% CI -6.1 to -0.2) with a trend for lower FEV1/FVC % predicted.
CONCLUSIONS:A genetic variant of PAI-1 together with early life LRI such as RSV bronchiolitis is associated with an increased risk of asthma, morbidity, and reduced lung function in this Latino population.
PLoS One. 2016 Aug 24;11(8):e0157848. doi: 10.1371/journal.pone.0157848. eCollection 2016.
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