Frequency of alleles and genotypes associated with alpha-1 antitrypsin deficiency in clinical and general populations: Revelations about underdiagnosis.

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 PI*S, PI*Z and 6 rare genetic variants. Certain deficiency genotypes were unevenly distributed among patients diagnosed with respiratory diseases: PI*ZZ (71.4%) and PI*SS (34.8%) genotypes were more represented in patients with chronic obstructive pulmonary disease (COPD), whereas PI*MZ (27.7%) and PI*SZ (34.5%) genotypes were more abundant in patients with bronchial asthma. The estimated frequency of PI*S and PI*Z alleles in the general population was 8.2% and 2.1%, respectively. A very significant enrichment (p< 0.01) of PI*S allele, independent of the PI*Z 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).

Hernández-Pérez JM ，Ramos-Díaz R ，Vaquerizo-Pollino C ，Pérez JA ... -  《Pulmonology》

The Distribution of Alpha-1 Antitrypsin Genotypes Between Patients with COPD/Emphysema, Asthma and Bronchiectasis.

Alpha-1-antitrypsin deficiency (AATD) is a rare hereditary condition characterized by low circulating levels of alpha-1antitrypsin (AAT). While the association between AATD and COPD/emphysema is undisputed, the association between AATD and asthma or bronchiectasis is still a matter of debate. Our study aimed to investigate the distribution of AAT genotypes between patients with COPD/emphysema, asthma and bronchiectasis. To back up the diagnostic labels, we described symptoms associated with the diagnosis. Between September 2003 and March 2020, 29,465 testing kits (AlphaKit®) were analyzed in the AAT laboratory, University of Marburg, Germany. The diagnosis of AATD has been made based on the measurements of AAT serum levels, followed by genotyping, phenotyping or whole gene sequencing depending on the availability and/or the need for more detailed interpretation of the results. The respiratory symptoms were recorded as well. Regarding the distribution of the wild type allele M and the most frequent mutations S (E264V) and Z (E342K), no significant differences could be found between COPD/emphysema [Pi*MM (58.24%); Pi*SZ (2.49%); Pi*ZZ (9.12%)] and bronchiectasis [Pi*MM (59.30%) Pi*SZ (2.81%); Pi*ZZ (7.02%)]. When COPD/emphysema and bronchiectasis were recorded in the same patient, the rate of Pi* ZZ (14.78%) mutations was even higher. Asthma patients exhibited significantly less deficient genotypes [Pi*MM (54.81%); Pi*SZ (2%); Pi*ZZ (2.77%)] than two other groups. Associated respiratory symptoms confirmed the diagnosis. COPD/emphysema and bronchiectasis, but not asthma patients, exhibit higher frequency of AATD genotypes. Our data suggest that AATD testing should be offered to patients with COPD/emphysema and bronchiectasis.

Veith M ，Tüffers J ，Peychev E ，Klemmer A ，Kotke V ，Janciauskiene S ，Wilhelm S ，Bals R ，Koczulla AR ，Vogelmeier CF ，Greulich T ... -  《International Journal of Chronic Obstructive Pulmonary Disease》

An Alpha-1 Antitrypsin Deficiency Screening Study in Patients with Chronic Obstructive Pulmonary Disease, Bronchiectasis, or Asthma in Turkey.

Tural Onur S ，Natoli A ，Dreger B ，Arınç S ，Sarıoğlu N ，Çörtük M ，Karadoğan D ，Şenyiğit A ，Yıldız BP ，Köktürk N ，Argun Barıs S ，Kodalak Cengiz S ，Polatli M ... -  《International Journal of Chronic Obstructive Pulmonary Disease》

The prevalence of PI*S and PI*Z SERPINA1 alleles in healthy individuals and COPD patients in Saudi Arabia: A case-control study.

Al-Jameil N ，Hassan AA ，Hassanato R ，Isac SR ，Otaiby MA ，Al-Shareef F ，Al-Maarik B ，Ajeyan IA ，Al-Bahloul K ，Ghani S ，Al-Torbak D ... -  《-》

Prevalence of alpha-1 antitrypsin deficiency and allele frequency in patients with COPD in Brazil.

Russo R ，Zillmer LR ，Nascimento OA ，Manzano B ，Ivanaga IT ，Fritscher L ，Lundgren F ，Miravitlles M ，Gondim HD ，Santos G Junior ，Alves MA ，Oliveira MV ，Souza AA ，Sales MP ，Jardim JR ... -  《-》