PNPLA3 and SERPINA1 Variants Are Associated with Severity of Fatty Liver Disease at First Referral to a Tertiary Center
Single nucleotide polymorphisms (SNPs), including <i>PNPLA3 rs738409</i> and <i>SERPINA1 rs17580,</i> have been identified as risk modifiers in the progression fatty liver disease (alcoholic (ALD) or non-alcoholic (NAFLD)). While <i>PNPLA3</i> has been studied in...
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MDPI AG
2021-03-01
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| Series: | Journal of Personalized Medicine |
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| Online Access: | https://www.mdpi.com/2075-4426/11/3/165 |
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| author | Georg Semmler Lorenz Balcar Hannes Oberkofler Stephan Zandanell Michael Strasser David Niederseer Alexandra Feldman Felix Stickel Pavel Strnad Christian Datz Bernhard Paulweber Elmar Aigner |
| author_facet | Georg Semmler Lorenz Balcar Hannes Oberkofler Stephan Zandanell Michael Strasser David Niederseer Alexandra Feldman Felix Stickel Pavel Strnad Christian Datz Bernhard Paulweber Elmar Aigner |
| author_sort | Georg Semmler |
| collection | DOAJ |
| description | Single nucleotide polymorphisms (SNPs), including <i>PNPLA3 rs738409</i> and <i>SERPINA1 rs17580,</i> have been identified as risk modifiers in the progression fatty liver disease (alcoholic (ALD) or non-alcoholic (NAFLD)). While <i>PNPLA3</i> has been studied in various settings, the value of both SNPs has so far not been addressed in a real-world cohort of subjects referred for a diagnostic work-up of liver disease. Thus, liver disease severity was assessed in 1257 consecutive patients with suspected ALD or NAFLD at the time of referral to a tertiary center. Advanced chronic liver disease (ACLD) was present in 309 (24.6%) patients and clinically significant portal hypertension (CSPH) was present in 185 (14.7%) patients. The <i>PNPLA3</i> G-allele was independently associated with a higher liver stiffness measurement (LSM; adjusted B: 2.707 (1.435–3.979), <i>p</i> < 0.001), and higher odds of ACLD (adjusted odds ratio (aOR): 1.971 (1.448–2.681), <i>p</i> < 0.001) and CSPH (aOR: 1.685 (1.180–2.406), <i>p</i> = 0.004). While the <i>SERPINA1</i> Z-allele was not associated with a higher LSM or the presence of ACLD, it was independently associated with higher odds of CSPH (aOR: 2.122 (1.067–4.218), <i>p</i> = 0.032). Associations of the <i>PNPLA3</i> G-allele and the <i>SERPINA1</i> Z-allele with CSPH were maintained independently of each other. The presence of both risk variants further increased the likelihood of ACLD and CSPH. |
| first_indexed | 2024-03-09T06:05:54Z |
| format | Article |
| id | doaj.art-f99414f282bb4165b0985ddf504118a0 |
| institution | Directory Open Access Journal |
| issn | 2075-4426 |
| language | English |
| last_indexed | 2024-03-09T06:05:54Z |
| publishDate | 2021-03-01 |
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| series | Journal of Personalized Medicine |
| spelling | doaj.art-f99414f282bb4165b0985ddf504118a02023-12-03T12:03:51ZengMDPI AGJournal of Personalized Medicine2075-44262021-03-0111316510.3390/jpm11030165PNPLA3 and SERPINA1 Variants Are Associated with Severity of Fatty Liver Disease at First Referral to a Tertiary CenterGeorg Semmler0Lorenz Balcar1Hannes Oberkofler2Stephan Zandanell3Michael Strasser4David Niederseer5Alexandra Feldman6Felix Stickel7Pavel Strnad8Christian Datz9Bernhard Paulweber10Elmar Aigner11First Department of Medicine, Paracelsus Medical University Salzburg, 5020 Salzburg, AustriaFirst Department of Medicine, Paracelsus Medical University Salzburg, 5020 Salzburg, AustriaDepartment of Laboratory Medicine, Paracelsus Medical University Salzburg, 5020 Salzburg, AustriaFirst Department of Medicine, Paracelsus Medical University Salzburg, 5020 Salzburg, AustriaFirst Department of Medicine, Paracelsus Medical University Salzburg, 5020 Salzburg, AustriaDepartment of Cardiology, University Heart Center Zurich, University Hospital Zurich, University of Zurich, 8006 Zurich, SwitzerlandFirst Department of Medicine, Paracelsus Medical University Salzburg, 5020 Salzburg, AustriaDepartment of Gastroenterology and Hepatology, University Hospital Zurich, University of Zurich, 8006 Zurich, SwitzerlandMedical Clinic III, Gastroenterology, Metabolic Diseases and Intensive Care, University Hospital RWTH Aachen, 52074 Aachen, GermanyDepartment of Internal Medicine, General Hospital Oberndorf, Teaching Hospital of the Paracelsus Medical University Salzburg, 5110 Oberndorf, AustriaFirst Department of Medicine, Paracelsus Medical University Salzburg, 5020 Salzburg, AustriaFirst Department of Medicine, Paracelsus Medical University Salzburg, 5020 Salzburg, AustriaSingle nucleotide polymorphisms (SNPs), including <i>PNPLA3 rs738409</i> and <i>SERPINA1 rs17580,</i> have been identified as risk modifiers in the progression fatty liver disease (alcoholic (ALD) or non-alcoholic (NAFLD)). While <i>PNPLA3</i> has been studied in various settings, the value of both SNPs has so far not been addressed in a real-world cohort of subjects referred for a diagnostic work-up of liver disease. Thus, liver disease severity was assessed in 1257 consecutive patients with suspected ALD or NAFLD at the time of referral to a tertiary center. Advanced chronic liver disease (ACLD) was present in 309 (24.6%) patients and clinically significant portal hypertension (CSPH) was present in 185 (14.7%) patients. The <i>PNPLA3</i> G-allele was independently associated with a higher liver stiffness measurement (LSM; adjusted B: 2.707 (1.435–3.979), <i>p</i> < 0.001), and higher odds of ACLD (adjusted odds ratio (aOR): 1.971 (1.448–2.681), <i>p</i> < 0.001) and CSPH (aOR: 1.685 (1.180–2.406), <i>p</i> = 0.004). While the <i>SERPINA1</i> Z-allele was not associated with a higher LSM or the presence of ACLD, it was independently associated with higher odds of CSPH (aOR: 2.122 (1.067–4.218), <i>p</i> = 0.032). Associations of the <i>PNPLA3</i> G-allele and the <i>SERPINA1</i> Z-allele with CSPH were maintained independently of each other. The presence of both risk variants further increased the likelihood of ACLD and CSPH.https://www.mdpi.com/2075-4426/11/3/165PNPLA3SERPINA1advanced chronic liver diseasecirrhosisNAFLDALD |
| spellingShingle | Georg Semmler Lorenz Balcar Hannes Oberkofler Stephan Zandanell Michael Strasser David Niederseer Alexandra Feldman Felix Stickel Pavel Strnad Christian Datz Bernhard Paulweber Elmar Aigner PNPLA3 and SERPINA1 Variants Are Associated with Severity of Fatty Liver Disease at First Referral to a Tertiary Center Journal of Personalized Medicine PNPLA3 SERPINA1 advanced chronic liver disease cirrhosis NAFLD ALD |
| title | PNPLA3 and SERPINA1 Variants Are Associated with Severity of Fatty Liver Disease at First Referral to a Tertiary Center |
| title_full | PNPLA3 and SERPINA1 Variants Are Associated with Severity of Fatty Liver Disease at First Referral to a Tertiary Center |
| title_fullStr | PNPLA3 and SERPINA1 Variants Are Associated with Severity of Fatty Liver Disease at First Referral to a Tertiary Center |
| title_full_unstemmed | PNPLA3 and SERPINA1 Variants Are Associated with Severity of Fatty Liver Disease at First Referral to a Tertiary Center |
| title_short | PNPLA3 and SERPINA1 Variants Are Associated with Severity of Fatty Liver Disease at First Referral to a Tertiary Center |
| title_sort | pnpla3 and serpina1 variants are associated with severity of fatty liver disease at first referral to a tertiary center |
| topic | PNPLA3 SERPINA1 advanced chronic liver disease cirrhosis NAFLD ALD |
| url | https://www.mdpi.com/2075-4426/11/3/165 |
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