PNPLA3 is the dominant SNP linked to liver disease severity at time of first referral to a tertiary center.

Autor: Balcar L; First Department of Medicine, Paracelsus Medical University Salzburg, Salzburg, Austria; Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria., Semmler G; First Department of Medicine, Paracelsus Medical University Salzburg, Salzburg, Austria; Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria; Department of Internal Medicine, General Hospital Oberndorf, Teaching Hospital of the Paracelsus Medical University Salzburg, Salzburg, Austria., Oberkofler H; First Department of Medicine, Paracelsus Medical University Salzburg, Salzburg, Austria., Zandanell S; First Department of Medicine, Paracelsus Medical University Salzburg, Salzburg, Austria., Strasser M; First Department of Medicine, Paracelsus Medical University Salzburg, Salzburg, Austria., Datz L; Department of Internal Medicine, General Hospital Oberndorf, Teaching Hospital of the Paracelsus Medical University Salzburg, Salzburg, Austria., Niederseer D; Department of Cardiology, University Hospital Zurich, Zurich, Switzerland., Feldman A; First Department of Medicine, Paracelsus Medical University Salzburg, Salzburg, Austria., Stickel F; Department of Gastroenterology and Hepatology, University Hospital Zurich, Zurich, Switzerland., Datz C; Department of Internal Medicine, General Hospital Oberndorf, Teaching Hospital of the Paracelsus Medical University Salzburg, Salzburg, Austria., Paulweber B; First Department of Medicine, Paracelsus Medical University Salzburg, Salzburg, Austria., Aigner E; First Department of Medicine, Paracelsus Medical University Salzburg, Salzburg, Austria. Electronic address: e.aigner@salk.at.
Jazyk: angličtina
Zdroj: Digestive and liver disease : official journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver [Dig Liver Dis] 2022 Jan; Vol. 54 (1), pp. 84-90. Date of Electronic Publication: 2021 Jul 11.
DOI: 10.1016/j.dld.2021.06.015
Abstrakt: Background: Single nucleotide polymorphisms (SNPs) in genes including PNPLA3, TM6SF2, HSD17B13 and SERPINA1 have been identified as risk modifiers of progression in chronic liver disease (CLD). However, it is unclear whether genotyping for these risk variants is useful in clinical routine.
Methods: Liver disease severity was assessed by liver stiffness measurement (LSM) and by presence of clinical manifestations of advanced-chronic liver disease (ACLD) in 779 consecutive CLD patients at the time of referral to a tertiary center. The associations of risk variants with CLD severity were calculated individually and in a combined model using a polygenic risk-score.
Results: Non-alcoholic fatty liver disease (NAFLD) was the most common etiology (n = 511, 65.6%), and ACLD was present in 217 (27.9%) patients. The PNPLA3-G-allele remained independently associated with higher LSM (adjusted-B: 2.508 [95%CI: 0.887-4.130], P = 0.002) or the presence of ACLD (aOR: 1.562 [95%CI: 1.097-2.226], P = 0.013). SERPINA1-Z-allele was also independently associated with LSM (adjusted-B: 4.558 [95%CI: 1.182-7.934], P = 0.008), while the other risk alleles did not attain statistical significance. Combining these risk alleles into a polygenic risk-score was significantly associated with LSM (adjusted-B: 0.948 [95%CI: 0.153-1.743], P = 0.020).
Conclusion: PNPLA3 risk-variants are linked to liver disease severity at the time of first referral to an outpatient hepatology clinic.
Competing Interests: Declaration of Competing Interest None of the authors have potential conflicts of interest with regard to this manuscript to disclose. However, some of the authors have conflicts of interest outside the submitted work: C.D. is part of the scientific advisor board of SPAR Österreich WarenhandelsAG.
(Copyright © 2021 The Author(s). Published by Elsevier Ltd.. All rights reserved.)
Databáze: MEDLINE
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