Interactions between SERPINA1 PiMZ genotype, occupational exposure and lung function decline.

Area of Science:

• Environmental Health
• Pulmonary Medicine
• Genetics

Background:

• The SERPINA1 PiMZ genotype is linked to intermediate alpha-1-antitrypsin deficiency.
• Occupational exposures to vapors, dusts, gases, and fumes (VGDF) and particulate matter (PM10) are known environmental risk factors for lung disease.
• Interactions between genetic predisposition and environmental exposures may influence lung function decline.

Purpose of the Study:

• To investigate the combined effects of the SERPINA1 PiMZ genotype, PM10 exposure, and VGDF exposure on annual lung function changes.
• To identify potential interactions between these factors in a large adult cohort.

Main Methods:

• Utilized spirometry data from 3739 adults in the Swiss Cohort Study on Air Pollution and Lung Disease in Adults (SAPALDIA).
• Employed linear mixed regression models to assess annual lung function change, evaluating interactions between PiMZ genotype and exposures (PM10, VGDF).
• Genotyping for SERPINA1 and detailed occupational exposure assessments were performed.

Main Results:

• Occupational VGDF exposure was associated with significant annual declines in FEF25-75% and FEV1/FVC, but only in PiMZ genotype carriers.
• A three-way interaction revealed that VGDF-associated FEF25-75% decline occurred specifically in ever-smoking PiMZ carriers.
• No significant interactions were found between the PiMZ genotype and outdoor PM10 exposure regarding lung function changes.

Conclusions:

• The SERPINA1 PiMZ genotype, particularly in individuals who smoke, modifies the impact of occupational VGDF exposure on lung function.
• These interactions highlight the complex interplay between genetic factors, lifestyle, and occupational environment in determining lung health.
• Further research and replication in larger cohorts are needed to confirm these findings.