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PNPLA3 GG Genotype and Carotid Atherosclerosis in Patients with Non-Alcoholic Fatty Liver Disease

BACKGROUND AND AIM: To evaluate if the presence of carotid atherosclerosis in patients with NAFLD, could be related to gene variants influencing hepatic fat accumulation and the severity of liver damage. METHODS: We recorded anthropometric, metabolic and histological data(Kleiner score) of 162 conse...

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Autores principales: Petta, Salvatore, Valenti, Luca, Marchesini, Giulio, Di Marco, Vito, Licata, Anna, Cammà, Calogero, Barcellona, Maria Rosa, Cabibi, Daniela, Donati, Benedetta, Fracanzani, Anna, Grimaudo, Stefania, Parrinello, Gaspare, Pipitone, Rosaria Maria, Torres, Daniele, Fargion, Silvia, Licata, Giuseppe, Craxì, Antonio
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3775795/
https://www.ncbi.nlm.nih.gov/pubmed/24069270
http://dx.doi.org/10.1371/journal.pone.0074089
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author Petta, Salvatore
Valenti, Luca
Marchesini, Giulio
Di Marco, Vito
Licata, Anna
Cammà, Calogero
Barcellona, Maria Rosa
Cabibi, Daniela
Donati, Benedetta
Fracanzani, Anna
Grimaudo, Stefania
Parrinello, Gaspare
Pipitone, Rosaria Maria
Torres, Daniele
Fargion, Silvia
Licata, Giuseppe
Craxì, Antonio
author_facet Petta, Salvatore
Valenti, Luca
Marchesini, Giulio
Di Marco, Vito
Licata, Anna
Cammà, Calogero
Barcellona, Maria Rosa
Cabibi, Daniela
Donati, Benedetta
Fracanzani, Anna
Grimaudo, Stefania
Parrinello, Gaspare
Pipitone, Rosaria Maria
Torres, Daniele
Fargion, Silvia
Licata, Giuseppe
Craxì, Antonio
author_sort Petta, Salvatore
collection PubMed
description BACKGROUND AND AIM: To evaluate if the presence of carotid atherosclerosis in patients with NAFLD, could be related to gene variants influencing hepatic fat accumulation and the severity of liver damage. METHODS: We recorded anthropometric, metabolic and histological data(Kleiner score) of 162 consecutive, biopsy-proven Sicilian NAFLD patients. Intima-media thickness(IMT), IMT thickening(IMT≥1 mm) and carotid plaques(focal thickening of >1.3 mm at the level of common carotid artery) were evaluated using ultrasonography. IL28B rs12979860 C>T, PNPLA3 rs738409 C>G, GCKR rs780094 C>T, LYPLAL1 rs12137855 C>T, and NCAN rs2228603 C>T single nucleotide polymorphisms were also assessed. The results were validated in a cohort of 267 subjects with clinical or histological diagnosis of NAFLD from Northern Italy, 63 of whom had follow-up examinations. RESULTS: Carotid plaques, IMT thickening and mean maximum IMT were similar in the two cohorts, whereas the prevalence of diabetes, obesity, NASH, and PNPLA3 GG polymorphism(21%vs.13%, p = 0.02) were significantly higher in the Sicilian cohort. In this cohort, the prevalence of carotid plaques and IMT thickening was higher in PNPLA3 GG compared to CC/CG genotype(53%vs.32%, p = 0.02; 62%vs.28%, p<0.001, respectively). These associations were confirmed at multivariate analyses (OR2.94;95%C.I. 1.12–7.71, p = 0.02, and OR4.11;95%C.I. 1.69–9.96, p = 0.002, respectively), although have been observed only in patients <50years. Also in the validation cohort, PNPLA3 GG genotype was independently associated with IMT thickening in younger patients only (OR: 6.00,95%C.I. 1.36–29, p = 0.01), and to IMT progression (p = 0.05) in patients with follow-up examinations. CONCLUSION: PNPLA3 GG genotype is associated with higher severity of carotid atherosclerosis in younger patients with NAFLD. Mechanisms underlying this association, and its clinical relevance need further investigations.
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spelling pubmed-37757952013-09-25 PNPLA3 GG Genotype and Carotid Atherosclerosis in Patients with Non-Alcoholic Fatty Liver Disease Petta, Salvatore Valenti, Luca Marchesini, Giulio Di Marco, Vito Licata, Anna Cammà, Calogero Barcellona, Maria Rosa Cabibi, Daniela Donati, Benedetta Fracanzani, Anna Grimaudo, Stefania Parrinello, Gaspare Pipitone, Rosaria Maria Torres, Daniele Fargion, Silvia Licata, Giuseppe Craxì, Antonio PLoS One Research Article BACKGROUND AND AIM: To evaluate if the presence of carotid atherosclerosis in patients with NAFLD, could be related to gene variants influencing hepatic fat accumulation and the severity of liver damage. METHODS: We recorded anthropometric, metabolic and histological data(Kleiner score) of 162 consecutive, biopsy-proven Sicilian NAFLD patients. Intima-media thickness(IMT), IMT thickening(IMT≥1 mm) and carotid plaques(focal thickening of >1.3 mm at the level of common carotid artery) were evaluated using ultrasonography. IL28B rs12979860 C>T, PNPLA3 rs738409 C>G, GCKR rs780094 C>T, LYPLAL1 rs12137855 C>T, and NCAN rs2228603 C>T single nucleotide polymorphisms were also assessed. The results were validated in a cohort of 267 subjects with clinical or histological diagnosis of NAFLD from Northern Italy, 63 of whom had follow-up examinations. RESULTS: Carotid plaques, IMT thickening and mean maximum IMT were similar in the two cohorts, whereas the prevalence of diabetes, obesity, NASH, and PNPLA3 GG polymorphism(21%vs.13%, p = 0.02) were significantly higher in the Sicilian cohort. In this cohort, the prevalence of carotid plaques and IMT thickening was higher in PNPLA3 GG compared to CC/CG genotype(53%vs.32%, p = 0.02; 62%vs.28%, p<0.001, respectively). These associations were confirmed at multivariate analyses (OR2.94;95%C.I. 1.12–7.71, p = 0.02, and OR4.11;95%C.I. 1.69–9.96, p = 0.002, respectively), although have been observed only in patients <50years. Also in the validation cohort, PNPLA3 GG genotype was independently associated with IMT thickening in younger patients only (OR: 6.00,95%C.I. 1.36–29, p = 0.01), and to IMT progression (p = 0.05) in patients with follow-up examinations. CONCLUSION: PNPLA3 GG genotype is associated with higher severity of carotid atherosclerosis in younger patients with NAFLD. Mechanisms underlying this association, and its clinical relevance need further investigations. Public Library of Science 2013-09-17 /pmc/articles/PMC3775795/ /pubmed/24069270 http://dx.doi.org/10.1371/journal.pone.0074089 Text en © 2013 Petta et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Petta, Salvatore
Valenti, Luca
Marchesini, Giulio
Di Marco, Vito
Licata, Anna
Cammà, Calogero
Barcellona, Maria Rosa
Cabibi, Daniela
Donati, Benedetta
Fracanzani, Anna
Grimaudo, Stefania
Parrinello, Gaspare
Pipitone, Rosaria Maria
Torres, Daniele
Fargion, Silvia
Licata, Giuseppe
Craxì, Antonio
PNPLA3 GG Genotype and Carotid Atherosclerosis in Patients with Non-Alcoholic Fatty Liver Disease
title PNPLA3 GG Genotype and Carotid Atherosclerosis in Patients with Non-Alcoholic Fatty Liver Disease
title_full PNPLA3 GG Genotype and Carotid Atherosclerosis in Patients with Non-Alcoholic Fatty Liver Disease
title_fullStr PNPLA3 GG Genotype and Carotid Atherosclerosis in Patients with Non-Alcoholic Fatty Liver Disease
title_full_unstemmed PNPLA3 GG Genotype and Carotid Atherosclerosis in Patients with Non-Alcoholic Fatty Liver Disease
title_short PNPLA3 GG Genotype and Carotid Atherosclerosis in Patients with Non-Alcoholic Fatty Liver Disease
title_sort pnpla3 gg genotype and carotid atherosclerosis in patients with non-alcoholic fatty liver disease
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3775795/
https://www.ncbi.nlm.nih.gov/pubmed/24069270
http://dx.doi.org/10.1371/journal.pone.0074089
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