Combining Genetic Variants to Improve Risk Prediction for NAFLD and Its Progression to Cirrhosis: A Proof of Concept Study

Umberto Vespasiani-Gentilucci, Chiara Dell'Unto, Antonio De Vincentis, Andrea Baiocchini, Marco Delle Monache, Roberto Cecere, Adriano Maria Pellicelli, Valerio Giannelli, Simone Carotti, Giovanni Galati, Paolo Gallo, Francesco Valentini, Franca Del Nonno, Davide Rosati, Sergio Morini, Raffaele Antonelli-Incalzi, Antonio Picardi

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Abstract

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.

Original languageEnglish
Article number7564835
JournalCanadian Journal of Gastroenterology and Hepatology
Volume2018
DOIs
Publication statusPublished - Jan 1 2018

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Fibrosis
Single Nucleotide Polymorphism
Non-alcoholic Fatty Liver Disease
Gene Frequency
Population

ASJC Scopus subject areas

  • Hepatology
  • Gastroenterology

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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.

In: Canadian Journal of Gastroenterology and Hepatology, Vol. 2018, 7564835, 01.01.2018.

Research output: Contribution to journalArticle

Vespasiani-Gentilucci, U, Dell'Unto, C, De Vincentis, A, Baiocchini, A, Delle Monache, M, Cecere, R, Pellicelli, AM, Giannelli, V, Carotti, S, Galati, G, Gallo, P, Valentini, F, Del Nonno, F, Rosati, D, Morini, S, Antonelli-Incalzi, R & Picardi, A 2018, 'Combining Genetic Variants to Improve Risk Prediction for NAFLD and Its Progression to Cirrhosis: A Proof of Concept Study', Canadian Journal of Gastroenterology and Hepatology, vol. 2018, 7564835. https://doi.org/10.1155/2018/7564835
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. In: Canadian Journal of Gastroenterology and Hepatology. 2018 ; Vol. 2018.
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T2 - A Proof of Concept Study

AU - Vespasiani-Gentilucci, Umberto

AU - Dell'Unto, Chiara

AU - De Vincentis, Antonio

AU - Baiocchini, Andrea

AU - Delle Monache, Marco

AU - Cecere, Roberto

AU - Pellicelli, Adriano Maria

AU - Giannelli, Valerio

AU - Carotti, Simone

AU - Galati, Giovanni

AU - Gallo, Paolo

AU - Valentini, Francesco

AU - Del Nonno, Franca

AU - Rosati, Davide

AU - Morini, Sergio

AU - Antonelli-Incalzi, Raffaele

AU - Picardi, Antonio

PY - 2018/1/1

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N2 - 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.

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