Alpha-1-antitrypsin phenotypes in adult liver disease patients

Ups J Med Sci. 2009;114(4):228-34. doi: 10.3109/03009730903243472.


Alpha-1-antitrypsin (AAT) is an important serine protease inhibitor in humans. Hereditary alpha-1-antitrypsin deficiency (AATD) affects lungs and liver. Liver disease caused by AATD in paediatric patients has been previously well documented. However, the association of liver disease with alpha-1-antitrypsin gene polymorphisms in adults is less clear. Therefore, we aimed to study AAT polymorphisms in adults with liver disease. We performed a case-control study. AAT polymorphisms were investigated by isoelectric focusing in 61 patients with liver cirrhosis and 9 patients with hepatocellular carcinoma. The control group consisted of 218 healthy blood donors. A significant deviation of observed and expected frequency of AAT phenotypes from Hardy-Weinberg equilibrium (chi-square = 34.77, df 11, P = 0.000) in the patient group was caused by a higher than expected frequency of Pi ZZ homozygotes (f = 0.0143 and f = 0.0005, respectively, P = 0.000). In addition, Pi M homozygotes were more frequent in patients than in controls (63% and 46%, respectively, P = 0.025). Our study results show that Pi ZZ homozygosity in adults could be associated with severe liver disease. Presence of Pi M homozygosity could be associated with liver disease via some mechanism different from Z allele-induced liver damage through accumulation of AAT polymers.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Alleles
  • Amino Acid Substitution
  • Carcinoma, Hepatocellular / blood
  • Carcinoma, Hepatocellular / genetics
  • Case-Control Studies
  • Female
  • Gene Frequency
  • Heterozygote
  • Homozygote
  • Humans
  • Liver Cirrhosis / blood
  • Liver Cirrhosis / etiology
  • Liver Cirrhosis / genetics
  • Liver Diseases / blood
  • Liver Diseases / etiology
  • Liver Diseases / genetics*
  • Liver Neoplasms / blood
  • Liver Neoplasms / genetics
  • Male
  • Middle Aged
  • Phenotype
  • Polymorphism, Genetic*
  • alpha 1-Antitrypsin / blood
  • alpha 1-Antitrypsin / genetics*
  • alpha 1-Antitrypsin Deficiency / blood
  • alpha 1-Antitrypsin Deficiency / complications
  • alpha 1-Antitrypsin Deficiency / genetics


  • SERPINA1 protein, human
  • alpha 1-Antitrypsin