α-1抗胰蛋白酶缺乏症及其变体与哮喘发作有关。 （注：原文中多了一个“and”）
Alpha-1 antitrypsin deficiency and and variants are associated with asthma exacerbations.
作者信息
Martín-González Elena, Hernández-Pérez José M, Pérez José A Pérez, Pérez-García Javier, Herrera-Luis Esther, González-Pérez Ruperto, González-González Orelvis, Mederos-Luis Elena, Sánchez-Machín Inmaculada, Poza-Guedes Paloma, Sardón Olaia, Corcuera Paula, Cruz María J, González-Barcala Francisco J, Martínez-Rivera Carlos, Mullol Joaquim, Muñoz Xavier, Olaguibel José M, Plaza Vicente, Quirce Santiago, Valero Antonio, Sastre Joaquín, Korta-Murua Javier, Del Pozo Victoria, Lorenzo-Díaz Fabián, Villar Jesús, Pino-Yanes María, González-Carracedo Mario A
机构信息
Genomics and Health Group, Department of Biochemistry, Microbiology, Cell Biology and Genetics, Universidad de La Laguna (ULL), 38200 La Laguna, Tenerife, Spain.
Department of Respiratory Medicine, Hospital Universitario de N.S de Candelaria, 38010 Santa Cruz de Tenerife, Spain.
出版信息
Pulmonology. 2025 Dec 31;31(1):2416870. doi: 10.1016/j.pulmoe.2023.05.002. Epub 2024 Oct 25.
INTRODUCTION AND OBJECTIVES
Asthma is a chronic inflammatory disease of the airways. Asthma patients may experience potentially life-threatening episodic flare-ups, known as exacerbations, which may significantly contribute to the asthma burden. The and variants of the gene, which usually involve alpha-1 antitrypsin (AAT) deficiency, had previously been associated with asthma. The link between AAT deficiency and asthma might be represented by the elastase/antielastase imbalance. However, their role in asthma exacerbations remains unknown. Our objective was to assess whether genetic variants and reduced AAT protein levels are associated with asthma exacerbations.
MATERIALS AND METHODS
In the discovery analysis, and variants and serum AAT levels were analyzed in 369 subjects from La Palma (Canary Islands, Spain). As replication, genomic data from two studies focused on 525 Spaniards and publicly available data from UK Biobank, FinnGen, and GWAS Catalog () were analyzed. The associations between and variants and AAT deficiency with asthma exacerbations were analyzed with logistic regression models, including age, sex, and genotype principal components as covariates.
RESULTS
In the discovery, a significant association with asthma exacerbations was found for both (odds ratio [OR]=2.38, 95% confidence interval [CI]= 1.40-4.04, -value=0.001) and (OR=3.49, 95%CI=1.55-7.85, -value=0.003)Likewise, AAT deficiency was associated with a higher risk for asthma exacerbations (OR=5.18, 95%CI=1.58-16.92, -value=0.007) as well as AAT protein levels (OR= 0.72, 95%CI=0.57-0.91, -value=0.005). The association with exacerbations was replicated in samples from Spaniards with two generations of Canary Islander origin (OR=3.79, -value=0.028), and a significant association with asthma hospitalizations was found in the Finnish population (OR=1.12, -value=0.007).
CONCLUSIONS
AAT deficiency could be a potential therapeutic target for asthma exacerbations in specific populations.
引言与目的
哮喘是一种气道慢性炎症性疾病。哮喘患者可能会经历潜在危及生命的发作性 flare-ups，即急性加重，这可能会显著增加哮喘负担。 基因的 和 变体通常与α-1抗胰蛋白酶（AAT）缺乏有关，此前已与哮喘相关联。AAT缺乏与哮喘之间的联系可能由弹性蛋白酶/抗弹性蛋白酶失衡来体现。然而，它们在哮喘急性加重中的作用仍不清楚。我们的目的是评估 基因变体和AAT蛋白水平降低是否与哮喘急性加重有关。
材料与方法
在发现分析中，对来自西班牙加那利群岛拉帕尔马岛的369名受试者的 和 变体以及血清AAT水平进行了分析。作为重复验证，分析了两项针对525名西班牙人的研究的基因组数据以及英国生物银行、芬兰基因库和全基因组关联研究目录（）的公开数据。使用逻辑回归模型分析 和 变体以及AAT缺乏与哮喘急性加重之间的关联，将年龄、性别和基因型主成分作为协变量。
结果
在发现分析中，发现 （比值比[OR]=2.38，95%置信区间[CI]=1.40 - 4.04， 值=0.001）和 （OR=3.49，95%CI=1.55 - 7.85， 值=0.003）均与哮喘急性加重显著相关。同样，AAT缺乏与哮喘急性加重风险较高（OR=5.18，95%CI=1.58 - 16.92， 值=0.007）以及AAT蛋白水平（OR=0.72，95%CI=0.57 - 0.91， 值=0.005）相关。 与急性加重的关联在有两代加那利岛原住民血统的西班牙人样本中得到重复验证（OR=3.79， 值=0.028），并且在芬兰人群中发现与哮喘住院存在显著关联（OR=1.12， 值=0.007）。
结论
AAT缺乏可能是特定人群中哮喘急性加重的一个潜在治疗靶点。
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