The PI*ZZ and PI*SS genotypes seem to be associated with chronic obstructive pulmonary disease (COPD) in patients with alpha-1 antitrypsin deficiency (AATD), according to a new study published in the Turkish Thoracic Journal.

In addition, tobacco use, low body weight, and older age increase the risk of COPD in people with the PI*MZ genotype, the same study found.

Respiratory diseases such as COPD are the main cause of morbidity and mortality in patients with AATD, especially those with the PI*ZZ genotype. However, it is not known whether there is a link between respiratory disease and other ATTD genotypes. 

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Here, a team of researchers led by José Antonio Pérez Pérez from the Department of Biochemistry, Microbiology, Cellular Biology and Genetics in the Canary Islands, Spain, sought to identify risk factors associated with respiratory diseases in the context of AATD. 

Read more about the comorbidities of AATD

To this end, they measured the lung function of 1334 people with a known genotype for the SERPINA1 gene and whose serum levels of alpha-1 antitrypsin (AAT) were known.

They found statistically significant associations between the PI*ZZ genotype and measures of lung function including abnormal forced expiratory volume in 1 second (FEV1); FEV1 over forced vital capacity (FVC), also known as the Tiffeneau-Pinelli index, which is used in the diagnosis of obstructive and restrictive lung diseases; and forced mid-expiratory flow between 25% and 75%. 

There were also significant associations between the PI*ZZ and PI*SS genotypes and COPD.

Finally, the prevalence of COPD was increased in people with the PI*MZ genotype who smoked, had a low body weight, or were older. 

AATD is a rare genetic disease characterized by obstructive lung disease and liver disease. It is caused by mutations in the SERPINA1 gene, which disrupt the normal production of AAT protein.


Hernández Pérez JM, Suárez Sánchez JJ, López Charry CV, Fariña YR, Pérez Pérez JA. Pulmonary function and respiratory diseases in different genotypes of alpha-1 antitrypsin deficiency. Turk Thorac J. Published online August 12, 2022. doi:10.5152/TurkThoracJ.2022.22001