What you carry at this position in your DNA and what research says about it.
Lung Health and COPD: 7/10 evidence, 35 publications.
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Sample genotype (not yours): T/T
Typical Lung Health and Normal COPD Risk
Two copies of the typical gene sequence mean normal levels of alpha-1 antitrypsin. This genotype is not associated with genetic lung or liver disease.
What this genotype means: Normal alpha-1 antitrypsin levels; Typical risk of COPD; Typical LDL cholesterol levels.
Sample genotype (not yours): A/A
Increased COPD Risk and Reduced Antitrypsin Levels
Two copies of the PiS variant result in moderately reduced alpha-1 antitrypsin levels. Avoiding smoking is critical to protect your lungs from progressive damage.
What this genotype means: Moderately reduced alpha-1 antitrypsin levels; Increased risk of COPD, especially with smoke exposure; Higher LDL cholesterol levels.
Sample genotype (not yours): T/A
Slightly Increased COPD Risk and Carrier Status
Carrying one copy of the PiS variant slightly reduces alpha-1 antitrypsin levels. While generally healthy, smoking can significantly increase your risk of lung issues.
What this genotype means: Mildly reduced alpha-1 antitrypsin levels; Slightly increased risk of COPD, especially if smoking; Slightly higher LDL cholesterol.
Gene function and biological role
Gene Function: The SERPINA1 gene encodes alpha-1 antitrypsin, a crucial protective protein produced mainly by the liver [1]. This protein circulates in the bloodstream and acts as a powerful inhibitor of neutrophil elastase, an enzyme that can destroy lung tissue [1]. When alpha-1 antitrypsin is deficient or structurally altered, the balance between proteases and antiproteases is disrupted, leaving the lungs vulnerable to progressive damage [1]. This gene is highly polymorphic, with several variants known to cause varying degrees of protein deficiency [2]. Severe deficiencies can lead to chronic obstructive pulmonary disease, emphysema, and liver complications [2].
Variant Impact: The rs17580 variant, commonly known as the S or PiS allele, is a missense mutation in the SERPINA1 gene [3]. This genetic change replaces the amino acid glutamate with valine at position 288 of the protein chain [3]. The structural alteration causes the resulting alpha-1 antitrypsin protein to be less stable, leading to increased intracellular degradation before it can be secreted [4]. Consequently, individuals carrying this variant have lower circulating levels of the protective protein in their blood [5]. While less severe than the notorious Z variant, the S variant still represents a significant risk modifier for respiratory health [5].
Key Insight: The PiS variant is the second most common deficiency allele in the SERPINA1 gene, but its impact on lung health is heavily influenced by environmental factors like smoking.
Location: SERPINA1. Chromosome 14 · 14q32.13 · 94.4 Mb
Estimated prevalence by population
Global 94.4%; European 91.9%; African 98.2%; East Asian 100.0%; South Asian 100.0%; Americas 89.3%; Ashkenazi 97.9%; Finnish 98.3%; Middle Eastern 100.0%; Amish 76.4%.
Estimated TT genotype frequency.
Global 5.5%; European 8.0%; African 1.7%; East Asian 0.0%; South Asian 0.0%; Americas 10.4%; Ashkenazi 2.1%; Finnish 1.6%; Middle Eastern 0.0%; Amish 22.0%.
Estimated TA genotype frequency.
Global 0.1%; European 0.2%; African < 0.1%; East Asian 0.0%; South Asian 0.0%; Americas 0.3%; Ashkenazi < 0.1%; Finnish < 0.1%; Middle Eastern 0.0%; Amish 1.6%.
Estimated AA genotype frequency.
Showing effects for T/T genotype
Organ Systems
Respiratory Health
COPD. Evidence: 7/10. Source: PMID 20301692. Typical Risk.
Alpha-1 Antitrypsin Levels. Evidence: 10/10. Source: PMID 22426792. Normal Levels.
Cardiovascular & Metabolic
Lipids & Cholesterol
LDL Cholesterol. Evidence: 10/10. Source: PMID 29507422. Typical Levels.
Blood Cell & Iron Traits
Platelet Count. Evidence: 10/10. Source: PMID 27863252. Typical Count.
Endocrine & Reproductive
Hormone Levels & Endocrine Regulation
SHBG Levels. Evidence: 10/10. Source: PMID 32042192. Typical Levels.
Showing effects for A/A genotype
COPD. Evidence: 7/10. Source: PMID 20301692. Increased Risk.
Alpha-1 Antitrypsin Levels. Evidence: 10/10. Source: PMID 22426792. Moderately Reduced.
LDL Cholesterol. Evidence: 10/10. Source: PMID 29507422. Higher LDL.
Platelet Count. Evidence: 10/10. Source: PMID 27863252. Higher Count.
SHBG Levels. Evidence: 10/10. Source: PMID 32042192. Higher SHBG.
Showing effects for T/A genotype
COPD. Evidence: 7/10. Source: PMID 20301692. Slightly Increased.
Alpha-1 Antitrypsin Levels. Evidence: 10/10. Source: PMID 22426792. Slightly Reduced.
LDL Cholesterol. Evidence: 10/10. Source: PMID 29507422. Slightly Higher.
Platelet Count. Evidence: 10/10. Source: PMID 27863252. Slightly Higher.
SHBG Levels. Evidence: 10/10. Source: PMID 32042192. Slightly Higher.
What this genotype means for the people who carry it
Sample genotype: TT (Homozygous)
Having the typical T/T genotype means you carry two normal copies of the SERPINA1 gene, often referred to as the PiMM genotype [1]. This genotype produces fully functional alpha-1 antitrypsin proteins at normal circulating levels [1]. These proteins effectively protect your lung tissue from being broken down by inflammatory enzymes [1]. As a result, you do not have the genetic predisposition to alpha-1 antitrypsin deficiency or the elevated risk of chronic obstructive pulmonary disease associated with this variant [2]. However, maintaining healthy lungs still depends heavily on avoiding smoking and environmental pollutants [2].
Normal alpha-1 antitrypsin levels; Typical risk of COPD; Typical LDL cholesterol levels.
Sample genotype: AA (Homozygous)
Carrying two copies of the A allele results in the PiSS genotype, which causes a moderate reduction in circulating alpha-1 antitrypsin levels to about 50-60% of normal [1]. While this is often enough to prevent spontaneous lung disease, it leaves very little reserve to handle inflammation [1]. Consequently, individuals with this genotype are at a significantly higher risk of developing chronic obstructive pulmonary disease, especially if they smoke or are exposed to environmental pollutants [2]. Unlike the more severe PiZZ genotype, the PiSS genotype is not typically associated with liver disease [3]. Protecting your respiratory system by avoiding tobacco smoke and air pollution is highly beneficial [2].
Moderately reduced alpha-1 antitrypsin levels; Increased risk of COPD, especially with smoke exposure; Higher LDL cholesterol levels.
Sample genotype: TA (Heterozygous)
Carrying one copy of the A allele means you are a carrier of the PiS variant, often referred to as having a PiMS genotype [1]. This genotype typically results in a mild reduction of circulating alpha-1 antitrypsin levels, down to about 80% of normal [2]. Under normal circumstances, this is still sufficient to protect your lungs from damage [2]. However, smoking or exposure to heavy dust and biomass smoke can overwhelm this protection, significantly increasing the risk of developing chronic obstructive pulmonary disease [3]. It is highly recommended to avoid smoking to preserve lung function [3].
Mildly reduced alpha-1 antitrypsin levels; Slightly increased risk of COPD, especially if smoking; Slightly higher LDL cholesterol.
Variants with shared genetic architecture
rs28929474 · SERPINA1 Gene · Chr 14 · Alpha-1 Antitrypsin Deficiency
rs112635299 · SERPINA1 Gene · Chr 14 · Lung and Liver Disease Risk
rs1303 · SERPINA1 Gene · Chr 14 · Lung Disease Risk
Alpha-1 Antitrypsin Deficiency.
Alpha1-antitrypsin deficiency.
Molecular abnormality of PI S variant of human alpha1-antitrypsin.
Serum levels and genotype distribution of α1-antitrypsin in the general population.
Content updated August 2026.
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