Servicio de Neumología del Hospital Universitario Nuestra Señora de Candelaria, Santa Cruz de Tenerife, Canary Islands, Spain.
Instituto Universitario de Enfermedades Tropicales y Salud Pública de Canarias, Universidad de La Laguna, Área de Genética. La Laguna, Tenerife, Spain.
Pulmonology. 2023 May-Jun;29(3):214-220. doi: 10.1016/j.pulmoe.2022.01.017. Epub 2022 Mar 26.
Alpha-1 antitrypsin deficiency (AATD) is an underdiagnosed hereditary condition that promotes the development of lung and liver diseases, and the most common potentially life-threatening genetic condition in Caucasian adults. In this study, the clinical and genetic profile of pulmonary patients from a single center in La Palma Island (Canary Islands, Spain) was assessed to predict how to increase AATD diagnosis.
AATD was tested in 1,493 pulmonary outpatients without regard to respiratory symptoms and 465 newborns. Variants of the SERPINA1 gene were characterised by real-time PCR, DNA sequencing, molecular haplotyping and phenotyping (AAT isoelectric focusing). Different respiratory pathologies were diagnosed in patients and their levels of serum AAT were measured by nephelometry.
The prevalence of pneumological patients with AATD alleles was 30.5%, including PIS, PIZ and 6 rare genetic variants. Certain deficiency genotypes were unevenly distributed among patients diagnosed with respiratory diseases: PIZZ (71.4%) and PISS (34.8%) genotypes were more represented in patients with chronic obstructive pulmonary disease (COPD), whereas PIMZ (27.7%) and PISZ (34.5%) genotypes were more abundant in patients with bronchial asthma. The estimated frequency of PIS and PIZ alleles in the general population was 8.2% and 2.1%, respectively. A very significant enrichment (p< 0.01) of PIS allele, independent of the PIZ allele, was detected in the clinical population.
AATD diagnosis would improve if both the COPD and the asthmatic patients were included to screening programs. The prevalence of PI*ZZ genotype in La Palma (1/2,162) was relatively high within Spain (average 1/3,344).
α-1 抗胰蛋白酶缺乏症（AATD）是一种未被充分诊断的遗传性疾病，可导致肺部和肝脏疾病的发生，是白种成年人中最常见的潜在危及生命的遗传疾病。在这项研究中，评估了来自西班牙拉帕尔马岛（加那利群岛）单一中心的肺部患者的临床和遗传特征，以预测如何增加 AATD 的诊断率。
在 1493 名无呼吸系统症状的肺科门诊患者和 465 名新生儿中检测了 AATD。通过实时 PCR、DNA 测序、分子单体型分析和表型（AAT 等电聚焦）对 SERPINA1 基因的变异进行了特征分析。对患者进行了不同的呼吸病理学诊断，并通过散射比浊法测量了其血清 AAT 水平。
携带 AATD 等位基因的肺科患者患病率为 30.5%，包括 PIS、PIZ 和 6 种罕见的遗传变异。某些缺陷基因型在诊断为呼吸系统疾病的患者中分布不均：PIZZ（71.4%）和 PISS（34.8%）基因型在慢性阻塞性肺疾病（COPD）患者中更为常见，而 PIMZ（27.7%）和 PISZ（34.5%）基因型在支气管哮喘患者中更为丰富。PIS 和 PIZ 等位基因在普通人群中的估计频率分别为 8.2%和 2.1%。在临床人群中，PIS 等位基因的丰度显著增加（p<0.01），与 PIZ 等位基因无关。
如果将 COPD 和哮喘患者都纳入筛查计划，AATD 的诊断率将会提高。在拉帕尔马（1/2162），PI*ZZ 基因型的流行率相对较高（西班牙平均为 1/3344）。
