title: Increased PiZ gene frequency for alpha 1 antitrypsin in patients with genetic haemochromatosis.
abstract: The putative relationship between genetic haemochromatosis and PiZ alpha 1 antitrypsin deficiency was studied using a monoclonal antibody against the PiZ variant in 67 consecutive patients with genetic haemochromatosis seen at Karolinska Hospital and Huddinge University Hospital, Stockholm over a 10 year period. Three (4.5%) of the patients with haemochromatosis were found to be PiZ homozygotes (odds ratio = 82, confidence interval = 26, 256; p < 0.0001). The prevalence of the heterozygous (PiZ) phenotype was similar to that in the general population (p = 0.937). During the ascertainment period, liver biopsy was performed in 65 (97%) of the patients; 66% (2 of 3) of the PiZ homozygotes were found to have cirrhosis compared with 10% (6/59) of the non-carriers of the PiZ variant (p = 0.039). None of the homozygous or heterozygous alpha 1 antitrypsin deficient patients had developed hepatocellular carcinoma compared with 3.4% (2 of 59) of the non-PiZ gene carriers (p = 1.0). Two of those with the homozygous phenotype had developed severe emphysema. HLA typing was performed in 18 patients, 16 (89%) of whom manifested antigens known to be linked to haemochromatosis. There were no significant differences between the PiZ gene carriers and non-carriers in mean age at onset of disease, sex distribution, or HLA type. Two of the PiZ heterozygotes had plasma alpha 1 antitrypsin concentrations below the normal range, though the group mean was lower than that of the non-PiZ carriers (p = 0.0003). The data suggest that the presence of the PiZ allele for alpha1 antitrypsin deficiency, in a double dose, is associated with genetic haemochromatosis and may contribute to the earlier onset of cirrhosis in these patients, though it does not increase the risk of hepatocellular carcinoma.
authors.affiliation: Department of Medicine, University of Lund, Malmö General Hospital, Sweden.
authors.forename: A N
authors.initials: AN
authors.lastname: Elzouki
authors.forename: R
authors.initials: R
authors.lastname: Hultcrantz
authors.forename: P
authors.initials: P
authors.lastname: Stål
authors.forename: R
authors.initials: R
authors.lastname: Befrits
authors.forename: S
authors.initials: S
authors.lastname: Eriksson
mesh_terms: D000328:Adult; D000368:Aged; D006528:Carcinoma, Hepatocellular / Q000235:genetics; D005260:Female; D005787:Gene Frequency; D006432:Hemochromatosis / Q000235:genetics*; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D008103:Liver Cirrhosis / Q000235:genetics; D008113:Liver Neoplasms / Q000235:genetics; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D019896:alpha 1-Antitrypsin Deficiency