α₁-Antitrypsin Gene Variation Associates With Asthma Exacerbations and Related Health Care Utilization

Area of Science:

• Genetics
• Pulmonology
• Environmental Health

Background:

• Alpha-1-antitrypsin deficiency, caused by SERPINA1 variants, is a key genetic risk factor for COPD.
• Few studies have explored SERPINA1's role in asthma severity, especially considering gene-environment interactions with smoking.

Purpose of the Study:

• To investigate how SERPINA1 variations influence asthma severity.
• To examine gene-environment interactions, particularly with smoking, in relation to asthma.

Main Methods:

• SERPINA1 resequencing was performed on DNA samples from white and African American participants in the Severe Asthma Research Program.
• Asthma severity was evaluated in an independent cohort using data from a Cleveland Clinic Health System database, including alpha-1-antitrypsin levels.

Main Results:

• In white individuals, SERPINA1 variants and smoking history interacted to increase asthma-related healthcare utilization, notably in PI type Z heterozygotes.
• PI type Z heterozygotes showed significantly higher rates of emergency department visits, hospitalizations, and ICU admissions compared to those without SERPINA1 variants.
• In African Americans, SERPINA1 variants and smoking showed a trend towards interaction for emergency department visits.
• Lower alpha-1-antitrypsin concentrations were associated with increased risk of moderate-to-severe asthma and exacerbations.

Conclusions:

• SERPINA1 variations and alpha-1-antitrypsin concentrations play a role in asthma severity.
• Gene-environment interactions between SERPINA1 variants and smoking are critical determinants of asthma outcomes.