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Titel: Liver Phenotypes of European Adults Heterozygous or Homozygous for Pi∗Z Variant of AAT (Pi∗MZ vs Pi∗ZZ genotype) and Noncarriers
VerfasserIn: Schneider, Carolin V.
Hamesch, Karim
Gross, Annika
Mandorfer, Mattias
Moeller, Linda S.
Pereira, Vitor
Pons, Monica
Kuca, Pawel
Reichert, Matthias C.
Benini, Federica
Burbaum, Barbara
Voss, Jessica
Gutberlet, Marla
Woditsch, Vivien
Lindhauer, Cecilia
Fromme, Malin
Kümpers, Julia
Bewersdorf, Lisa
Schaefer, Benedikt
Eslam, Mohammed
Bals, Robert
Janciauskiene, Sabina
Carvão, Joana
Neureiter, Daniel
Zhou, Biaohuan
Wöran, Katharina
Bantel, Heike
Geier, Andreas
Dirrichs, Timm
Stickel, Felix
Teumer, Alexander
Verbeek, Jef
Nevens, Frederik
Govaere, Olivier
Krawczyk, Marcin
Roskams, Tania
Haybaeck, Johannes
Lurje, Georg
Chorostowska-Wynimko, Joanna
Genesca, Joan
Reiberger, Thomas
Lammert, Frank
Krag, Aleksander
George, Jacob
Anstee, Quentin M.
Trauner, Michael
Datz, Christian
Gaisa, Nadine T.
Denk, Helmut
Trautwein, Christian
Aigner, Elmar
Strnad, Pavel
Sprache: Englisch
Titel: Gastroenterology
Bandnummer: 159
Heft: 2
Seiten: 534-548
Verlag/Plattform: Elsevier
Erscheinungsjahr: 2020
DDC-Sachgruppe: 610 Medizin, Gesundheit
Dokumenttyp: Journalartikel / Zeitschriftenartikel
Abstract: 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.
DOI der Erstveröffentlichung: 10.1053/j.gastro.2020.04.058
URL der Erstveröffentlichung: https://www.sciencedirect.com/science/article/abs/pii/S0016508520305771
Link zu diesem Datensatz: urn:nbn:de:bsz:291--ds-367905
hdl:20.500.11880/33425
http://dx.doi.org/10.22028/D291-36790
ISSN: 0016-5085
Datum des Eintrags: 12-Jul-2022
Fakultät: M - Medizinische Fakultät
Fachrichtung: M - Innere Medizin
Professur: M - Prof. Dr. Robert Bals
M - Prof. Dr. Frank Lammert
Sammlung:SciDok - Der Wissenschaftsserver der Universität des Saarlandes

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