title: Alpha-1-antitrypsin phenotypes in adult liver disease patients.
abstract: 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.
authors: Institute of Medical Biochemistry, Faculty of Pharmacy, University of Belgrade, Belgrade, Serbia. atopic@pharmacy.bg.ac.rs
authors: Aleksandra
authors: A
authors: Topic
authors: Tamara
authors: T
authors: Alempijevic
authors: Aleksandra Sokic
authors: AS
authors: Milutinovic
authors: Nada
authors: N
authors: Kovacevic
mesh_terms: D000328:Adult; D000368:Aged; D000483:Alleles; D019943:Amino Acid Substitution; D006528:Carcinoma, Hepatocellular / Q000097:blood / Q000235:genetics; D016022:Case-Control Studies; D005260:Female; D005787:Gene Frequency; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D008103:Liver Cirrhosis / Q000097:blood / Q000209:etiology / Q000235:genetics; D008107:Liver Diseases / Q000097:blood / Q000209:etiology / Q000235:genetics*; D008113:Liver Neoplasms / Q000097:blood / Q000235:genetics; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D011110:Polymorphism, Genetic; D000515:alpha 1-Antitrypsin / Q000097:blood / Q000235:genetics*; D019896:alpha 1-Antitrypsin Deficiency / Q000097:blood / Q000150:complications / Q000235:genetics
chemical_list: C043392:SERPINA1 protein, human; D000515:alpha 1-Antitrypsin