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Alpha-1 antitrypsin deficiency DNA test

Alpha-1 antitrypsin deficiency DNA test:

Alpha-1 antitrypsin (A1A) is a protein produced by the liver and, in smaller quantities, also by the lung epithelium and macrophages. With circulation, A1A enters the lungs, where it performs its functions.

The most common genetic cause of A1A deficiency is mutations of the SERPINA1 gene, which results in inadequate, degraded or dysfunctional protein entering the circulation. PI-M variants are not related to the A1A deficiency, but two of the most common mutations causing these pathologies have been described:

PI-S (rs17580, NM_001127701.1(SERPINA1):c.863A>T (p.Glu288Val))

PI-Z (rs28929474, NM_001127701.1(SERPINA1):c.1096G>A (p.Glu366Lys)).

The disease is found in about 1:3000-1:5000

Type of heredity: autosomal codominant

Testing goal: To determine the presence of the two most common (PI-S and PI-Z) SERPINA1 gene mutations in the genome in patients with clinically suspected A1A deficiency

Interpretation of test results:

MM – normal genotype, 100% A1A level

MS – 80% of normal A1A level

SS – 60% of normal A1A level

MZ – 55% of normal A1A level; in some studies, this genotype is statistically more common in the group of cryptogenic liver cirrhosis

SZ – 40% of normal A1A level; increased risk of lung and liver disease

ZZ – 15% of normal A1A level; clinically most prominent phenotype associated with early pulmonary emphysema (among approximately 35-year-old individuals), cryptogenic liver cirrhosis, juvenile liver cirrhosis, hepatocellular carcinoma

ZZ or SZ genotype – clinical manifestations of A1A.

For whom is this test intended? The test is intended for individuals with serologically determined lowered A1A level – to determine the status of mutations.

  1. The WHO recommends that all individuals with chronic obstructive pulmonary disease (COPD), as well as adults and adolescents with asthma be serologically tested.
  2. If there are clinical signs of A1A deficiency – emphysema in 3rd or 4th decade, emphysema in a non-smoker, family history of emphysema, emphysema in lower lung lobes (Rtg), adult-onset asthma, common bronchitis.
  3. Serological testing is recommended for patients with chronic, recurrent respiratory symptoms (dyspnoea, cough, etc.).

Genetic testing is recommended if serum is found to be low in A1A.

Recommendations for carriers of PI-SZ and PI-ZZ genotype:

  • Vaccination against influenza and pneumococci to protect the lungs from further damage
  • Visit a doctor immediately if you have symptoms of cold; these symptoms should be treated fairly aggressively
  • Avoid smoking (both active and passive), corrosive gases, dust, contamination
  • Do sports on a regular basis
  • Check liver health
  • If necessary, take A1A substitution intravenously

Mutation testing method DNA extraction, PCR, Sanger sequencing of the regions of SERPINA1 gene containing mutations


  • Other very rare mutations in the SERPINA1 gene that cause A1A deficiency are also possible; with this test it is impossible to detect them.
  • In rare cases, false negative results may be due to the possibility of mutations at the site of attachment of oligonucleotides (PCR primers).