Structure and variation of human alpha 1-antitrypsin

Area of Science:

• Biochemistry
• Pulmonology
• Genetics

Background:

• Alpha 1-antitrypsin (AAT) functions as a critical scavenger of leukocyte elastase in tissues.
• Genetic variants of AAT are prevalent in European populations.
• AAT deficiency predisposes individuals to progressive lung elasticity loss.

Purpose of the Study:

• To elucidate the role of alpha 1-antitrypsin sequence in its scavenger function.
• To understand the genetic basis of AAT deficiency and its link to lung disease.
• To investigate the impact of cigarette smoking on AAT deficiency and emphysema development.

Main Methods:

• Sequence analysis of alpha 1-antitrypsin.
• Identification and characterization of abnormal AAT variants.
• Correlation of genetic deficiency with disease progression and environmental factors.

Main Results:

• The sequence of AAT aligns with its elastase-scavenging role.
• Two common abnormal variants in Europeans result in AAT deficiency.
• This deficiency leads to a progressive loss of lung elasticity.

Conclusions:

• The reactive center of AAT is key to understanding its interaction with elastase.
• Cigarette smoking exacerbates AAT deficiency, accelerating emphysema onset and severity.
• AAT deficiency represents a significant risk factor for developing emphysema, particularly in smokers.