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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
medicine
Liver Phenotypes of European Adults Heterozygous or Homozygous for Pi∗Z Variant of AAT (Pi∗MZ vs Pi∗ZZ genotype) and Noncarriers
Gastroenterology, Volume 159, No. 2, Year 2020
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Description
Background & Aims: Homozygosity for the Pi∗Z variant of the gene that encodes the alpha-1 antitrypsin peptide (AAT), called the Pi∗ZZ genotype, causes a liver and lung disease called alpha-1 antitrypsin deficiency. Heterozygosity (the Pi∗MZ genotype) is a risk factor for cirrhosis in individuals with liver disease. Up to 4% of Europeans have the Pi∗MZ genotype; we compared features of adults with and without Pi∗MZ genotype among persons without preexisting liver disease. Methods: We analyzed data from the European Alpha-1 Liver Cohort, from 419 adults with the Pi∗MZ genotype, 309 adults with the Pi∗ZZ genotype, and 284 individuals without the variant (noncarriers). All underwent a comprehensive evaluation; liver stiffness measurements (LSMs) were made by transient elastography. Liver biopsies were analyzed to define histologic and biochemical features associated with the Pi∗Z variant. Levels of serum transaminases were retrieved from 444,642 participants, available in the United Kingdom biobank. Results: In the UK biobank database, levels of serum transaminases were increased in subjects with the Pi∗MZ genotype compared with noncarriers. In the Alpha-1 Liver Cohort, adults with Pi∗MZ had lower levels of gamma-glutamyl transferase in serum and lower LSMs than adults with the Pi∗ZZ variant, but these were higher than in noncarriers. Ten percent of subjects with the Pi∗MZ genotype vs 4% of noncarriers had LSMs of 7.1 kPa or more (adjusted odds ratio, 4.8; 95% confidence interval, 2.0–11.8). Obesity and diabetes were the most important factors associated with LSMs ≥7.1 kPa in subjects with the Pi∗MZ genotype. AAT inclusions were detected in liver biopsies of 63% of subjects with the Pi∗MZ genotype, vs 97% of subjects with the Pi∗ZZ genotype, and increased with liver fibrosis stages. Subjects with the Pi∗MZ genotype did not have increased hepatic levels of AAT, whereas levels of insoluble AAT varied among individuals. Conclusions: Adults with the Pi∗MZ genotype have lower levels of serum transaminases, fewer AAT inclusions in liver, and lower liver stiffness than adults with the Pi∗ZZ genotype, but higher than adults without the Pi∗Z variant. These findings should help determine risk of subjects with the Pi∗MZ genotype and aid in counseling. © 2020 AGA Institute
Authors & Co-Authors
Schneider, Carolin Victoria
Germany, Aachen
Uniklinik Rwth Aachen
Hamesch, Karim
Germany, Aachen
Uniklinik Rwth Aachen
Mandorfer, Mattias
Austria, Vienna
Medizinische Universität Wien
Lindhauer, Cecilia
Germany, Aachen
Uniklinik Rwth Aachen
Fromme, Malin
Germany, Aachen
Uniklinik Rwth Aachen
Eslam, Mohammed
Australia, Parramatta
The Westmead Institute for Medical Research
Bals, Robert
Germany, Homburg
Universitätsklinikum Des Saarlandes Medizinische Fakultät Der Universität Des Saarlandes
Zhou, Biaohuan
Germany, Aachen
Uniklinik Rwth Aachen
Bantel, Heike
Germany, Hannover
Hannover Medical School
Geier, Andreas
Germany, Wurzburg
Julius-maximilians-universität Würzburg
Stickel, Felix
Switzerland, Zurich
Universitatsspital Zurich
Teumer, Alexander
Germany, Greifswald
Universitätsmedizin Greifswald
Germany, Berlin
Deutsches Zentrum Für Herz-kreislauf-forschung E. V.
Nevens, Frederik
Belgium, Leuven
Ku Leuven
Govaere, Olivier
United Kingdom, Newcastle
Newcastle University
United Kingdom, Newcastle
The Newcastle Upon Tyne Hospitals Nhs Foundation Trust
Krawczyk, Marcin
Germany, Homburg
Universitätsklinikum Des Saarlandes Medizinische Fakultät Der Universität Des Saarlandes
Poland, Warsaw
Medical University of Warsaw
Roskams, Tania A.D.
Belgium, Leuven
Ku Leuven
Haybaeck, Johannes
Austria, Innsbruck
Medizinische Universitat Innsbruck
Austria, Graz
Medizinische Universität Graz
Lurje, Georg
Germany, Aachen
Uniklinik Rwth Aachen
Germany, Berlin
Charité – Universitätsmedizin Berlin
Chorostowska-Wynimko, Joanna
Poland, Warsaw
National Institute of Tuberculosis and Lung Diseases, Warszawa
Genescá, Joan
Spain, Cerdanyola Del Valles
Universitat Autònoma de Barcelona
Spain, Madrid
Instituto de Salud Carlos Iii
Reiberger, Thomas
Austria, Vienna
Medizinische Universität Wien
Lammert, Frank
Germany, Homburg
Universitätsklinikum Des Saarlandes Medizinische Fakultät Der Universität Des Saarlandes
Krag, Aleksander Ahm
Denmark, Odense
Odense Universitetshospital
George, Jacob A.
Australia, Parramatta
The Westmead Institute for Medical Research
Anstee, Quentin M.
United Kingdom, Newcastle
Newcastle University
United Kingdom, Newcastle
The Newcastle Upon Tyne Hospitals Nhs Foundation Trust
Trauner, Michael A.
Austria, Vienna
Medizinische Universität Wien
Trautwein, Christian
Germany, Aachen
Uniklinik Rwth Aachen
Aigner, Elmar S.
Austria, Salzburg
Paracelsus Medizinische Privatuniversitat
Strnad, Pavel
Germany, Aachen
Uniklinik Rwth Aachen
Statistics
Citations: 52
Authors: 29
Affiliations: 24
Identifiers
Doi:
10.1053/j.gastro.2020.04.058
ISSN:
00165085
Research Areas
Genetics And Genomics
Noncommunicable Diseases
Study Design
Cohort Study
Case-Control Study