The following is a summary of “Frequency of alleles and genotypes associated with alpha-1 antitrypsin deficiency in clinical and general populations: Revelations about underdiagnosis,” published in the May–June 2023 issue of Pulmonology by Pérez, et al.
Alpha-1 antitrypsin deficiency (AATD) is a hereditary condition that is often undiagnosed but can lead to the development of lung and liver diseases. It was considered the most common potentially life-threatening genetic condition among Caucasian adults. For a study, researchers sought to assess the clinical and genetic profile of pulmonary patients in a single center on La Palma Island, Canary Islands, Spain, to identify strategies to increase AATD diagnosis.
A total of 1,493 pulmonary outpatients and 465 newborns were tested for AATD regardless of respiratory symptoms. Variants of the SERPINA1 gene, associated with AATD, were characterized using real-time PCR, DNA sequencing, molecular haplotyping, and phenotyping (AAT isoelectric focusing). Different respiratory pathologies were diagnosed in the patients, and their serum AAT levels were measured using nephelometry.
The prevalence of AATD alleles among pneumological patients was 30.5%, including common variants such as PI*S and PI*Z and six rare genetic variants. Specific deficiency genotypes were found to be unevenly distributed among patients diagnosed with respiratory diseases. The PI*ZZ genotype was more prevalent in patients with chronic obstructive pulmonary disease (COPD), accounting for 71.4% of cases. In comparison, the PISS genotype was more common in COPD patients, with a prevalence of 34.8%. On the other hand, the PI*MZ genotype (27.7%) and PI*SZ genotype (34.5%) 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. Significant enrichment of the PI*S allele, independent of the PI*Z allele, was observed in the clinical population.
The diagnosis of AATD could be improved by including both COPD and asthmatic patients in screening programs. The prevalence of the PI*ZZ genotype on La Palma Island (1 in 2,162 individuals) was relatively high compared to the average prevalence in Spain (1 in 3,344 individuals). The findings highlighted the importance of increasing awareness and diagnosis of AATD in the population, particularly among patients with respiratory diseases, to provide appropriate management and treatment.
Source: sciencedirect.com/science/article/pii/S2531043722000307