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Combining Genetic Variants to Improve Risk Prediction for NAFLD and Its Progression to Cirrhosis: A Proof of Concept Study
BACKGROUND & AIMS: Identifying NAFLD patients at risk of progression is crucial to orient medical care and resources. We aimed to verify if the effects determined by different single nucleotide polymorphisms (SNPs) could add up to multiply the risk of NAFLD and NASH-cirrhosis. METHODS: Three stu...
Autores principales: | , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Hindawi
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5872672/ https://www.ncbi.nlm.nih.gov/pubmed/29732362 http://dx.doi.org/10.1155/2018/7564835 |
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author | Vespasiani-Gentilucci, Umberto Dell'Unto, Chiara De Vincentis, Antonio Baiocchini, Andrea Delle Monache, Marco Cecere, Roberto Pellicelli, Adriano Maria Giannelli, Valerio Carotti, Simone Galati, Giovanni Gallo, Paolo Valentini, Francesco Del Nonno, Franca Rosati, Davide Morini, Sergio Antonelli-Incalzi, Raffaele Picardi, Antonio |
author_facet | Vespasiani-Gentilucci, Umberto Dell'Unto, Chiara De Vincentis, Antonio Baiocchini, Andrea Delle Monache, Marco Cecere, Roberto Pellicelli, Adriano Maria Giannelli, Valerio Carotti, Simone Galati, Giovanni Gallo, Paolo Valentini, Francesco Del Nonno, Franca Rosati, Davide Morini, Sergio Antonelli-Incalzi, Raffaele Picardi, Antonio |
author_sort | Vespasiani-Gentilucci, Umberto |
collection | PubMed |
description | BACKGROUND & AIMS: Identifying NAFLD patients at risk of progression is crucial to orient medical care and resources. We aimed to verify if the effects determined by different single nucleotide polymorphisms (SNPs) could add up to multiply the risk of NAFLD and NASH-cirrhosis. METHODS: Three study populations, that is, patients diagnosed with NASH-cirrhosis or with noncirrhotic NAFLD and healthy controls, were enrolled. PNPLA3 rs738409, TM6SF2 rs58542926, KLF6 rs3750861, SOD2 rs4880, and LPIN1 rs13412852 were genotyped. RESULTS: One hundred and seven NASH-cirrhotics, 93 noncirrhotic NAFLD, and 90 controls were enrolled. At least one difference in allele frequency between groups was significant, or nearly significant, for the PNPLA3, TM6SF2, and KLF6 variants (p < 0.001, p < 0.05, and p = 0.06, resp.), and a risk score based on these SNPs was generated. No differences were observed for SOD2 and LPIN1 SNPs. When compared to a score of 0, a score of 1-2 quadrupled, and a score of 3-4 increased 20-fold the risk of noncirrhotic NAFLD; a score of 3-4 quadrupled the risk of NASH-cirrhosis. CONCLUSIONS: The effects determined by disease-associated variants at different loci can add up to multiply the risk of NAFLD and NASH-cirrhosis. Combining different disease-associated variants may represent the way for genetics to keep strength in NAFLD diagnostics. |
format | Online Article Text |
id | pubmed-5872672 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Hindawi |
record_format | MEDLINE/PubMed |
spelling | pubmed-58726722018-05-06 Combining Genetic Variants to Improve Risk Prediction for NAFLD and Its Progression to Cirrhosis: A Proof of Concept Study Vespasiani-Gentilucci, Umberto Dell'Unto, Chiara De Vincentis, Antonio Baiocchini, Andrea Delle Monache, Marco Cecere, Roberto Pellicelli, Adriano Maria Giannelli, Valerio Carotti, Simone Galati, Giovanni Gallo, Paolo Valentini, Francesco Del Nonno, Franca Rosati, Davide Morini, Sergio Antonelli-Incalzi, Raffaele Picardi, Antonio Can J Gastroenterol Hepatol Research Article BACKGROUND & AIMS: Identifying NAFLD patients at risk of progression is crucial to orient medical care and resources. We aimed to verify if the effects determined by different single nucleotide polymorphisms (SNPs) could add up to multiply the risk of NAFLD and NASH-cirrhosis. METHODS: Three study populations, that is, patients diagnosed with NASH-cirrhosis or with noncirrhotic NAFLD and healthy controls, were enrolled. PNPLA3 rs738409, TM6SF2 rs58542926, KLF6 rs3750861, SOD2 rs4880, and LPIN1 rs13412852 were genotyped. RESULTS: One hundred and seven NASH-cirrhotics, 93 noncirrhotic NAFLD, and 90 controls were enrolled. At least one difference in allele frequency between groups was significant, or nearly significant, for the PNPLA3, TM6SF2, and KLF6 variants (p < 0.001, p < 0.05, and p = 0.06, resp.), and a risk score based on these SNPs was generated. No differences were observed for SOD2 and LPIN1 SNPs. When compared to a score of 0, a score of 1-2 quadrupled, and a score of 3-4 increased 20-fold the risk of noncirrhotic NAFLD; a score of 3-4 quadrupled the risk of NASH-cirrhosis. CONCLUSIONS: The effects determined by disease-associated variants at different loci can add up to multiply the risk of NAFLD and NASH-cirrhosis. Combining different disease-associated variants may represent the way for genetics to keep strength in NAFLD diagnostics. Hindawi 2018-03-14 /pmc/articles/PMC5872672/ /pubmed/29732362 http://dx.doi.org/10.1155/2018/7564835 Text en Copyright © 2018 Umberto Vespasiani-Gentilucci et al. https://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Article Vespasiani-Gentilucci, Umberto Dell'Unto, Chiara De Vincentis, Antonio Baiocchini, Andrea Delle Monache, Marco Cecere, Roberto Pellicelli, Adriano Maria Giannelli, Valerio Carotti, Simone Galati, Giovanni Gallo, Paolo Valentini, Francesco Del Nonno, Franca Rosati, Davide Morini, Sergio Antonelli-Incalzi, Raffaele Picardi, Antonio Combining Genetic Variants to Improve Risk Prediction for NAFLD and Its Progression to Cirrhosis: A Proof of Concept Study |
title | Combining Genetic Variants to Improve Risk Prediction for NAFLD and Its Progression to Cirrhosis: A Proof of Concept Study |
title_full | Combining Genetic Variants to Improve Risk Prediction for NAFLD and Its Progression to Cirrhosis: A Proof of Concept Study |
title_fullStr | Combining Genetic Variants to Improve Risk Prediction for NAFLD and Its Progression to Cirrhosis: A Proof of Concept Study |
title_full_unstemmed | Combining Genetic Variants to Improve Risk Prediction for NAFLD and Its Progression to Cirrhosis: A Proof of Concept Study |
title_short | Combining Genetic Variants to Improve Risk Prediction for NAFLD and Its Progression to Cirrhosis: A Proof of Concept Study |
title_sort | combining genetic variants to improve risk prediction for nafld and its progression to cirrhosis: a proof of concept study |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5872672/ https://www.ncbi.nlm.nih.gov/pubmed/29732362 http://dx.doi.org/10.1155/2018/7564835 |
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