Relationship Between Methylome and Transcriptome in Patients With Nonalcoholic Fatty Liver Disease
Open accessAbstract
Background & aims Cirrhosis and liver cancer are potential outcomes of advanced nonalcoholic fatty liver disease (NAFLD). It is not clear what factors determine whether patients will develop advanced or mild NAFLD, limiting noninvasive diagnosis and treatment before clinical sequelae emerge. We investigated whether DNA methylation profiles can distinguish patients with mild disease from those with advanced NAFLD, and how these patterns are functionally related to hepatic gene expression.Methods We collected frozen liver biopsies and clinical data from patients with biopsy-proven NAFLD (56 in the discovery cohort and 34 in the replication cohort). Samples were divided into groups based on histologic severity of fibrosis: F0-1 (mild) and F3-4 (advanced). DNA methylation profiles were determined and coupled with gene expression data from the same biopsies; differential methylation was validated in subsets of the discovery and replication cohorts. We then analyzed interactions between the methylome and transcriptome.Results Clinical features did not differ between patients known to have mild or advanced fibrosis based on biopsy analysis. There were 69,247 differentially methylated CpG sites (76% hypomethylated, 24% hypermethylated) in patients with advanced vs mild NAFLD (P < .05). Methylation at fibroblast growth factor receptor 2, methionine adenosyl methyltransferase 1A, and caspase 1 was validated by bisulfite pyrosequencing and the findings were reproduced in the replication cohort. Methylation correlated with gene transcript levels for 7% of differentially methylated CpG sites, indicating that differential methylation contributes to differences in expression. In samples with advanced NAFLD, many tissue repair genes were hypomethylated and overexpressed, and genes in certain metabolic pathways, including 1-carbon metabolism, were hypermethylated and underexpressed.Conclusions Functionally relevant differences in methylation can distinguish patients with advanced vs mild NAFLD. Altered methylation of genes that regulate processes such as steatohepatitis, fibrosis, and carcinogenesis indicate the role of DNA methylation in progression of NAFLD.
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DNA methylation patterns at fibrosis-related genes such as TGFβ1, COL1A1, PDGFα, PPARα, and PPARδ can distinguish mild from advanced MASLD and predict future fibrosis progression.
“Moreover, certain patterns of DNA methylation at fibrosis-related genes, such as those encoding TGFβ1, COL1A1, PDGFα, peroxisome proliferator-activated receptor alpha (PPARα), and peroxisome proliferator-activated receptor delta (PPARδ), can not only distinguish between patients with mild versus advanced MASLD, but also predict future fibrosis progression (169-172).”
From Found in translation—Fibrosis in metabolic dysfunction–associated steatohepatitis (MASH) (2023) · cites this paper as [169]
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Bioconductor: open software development for computational biology and bioinformatics
Gentleman, R., Carey, V., Bates, D., Bolstad, B., Dettling, M., Dudoit, S., Ellis, B., Gautier, L., Ge, Y., Gentry, J., et al. (2004) · Genome Biology · doi:10.1186/gb-2004-5-10-r80 · Cited by 13,133 · see citing works
Chalasani, N., Younossi, Z. M., Lavine, J. E., Diehl, A. M., Brunt, E. M., Cusi, K. J., Charlton, M., & Sanyal, A. J. (2012) · Hepatology · doi:10.1002/hep.25762 · Cited by 3,805 · see citing works
Self-citationDNA methylation and human disease
Robertson, K. D. (2005) · Nature Reviews Genetics · doi:10.1038/nrg1655 · Cited by 2,864 · see citing works
The accessible chromatin landscape of the human genome
Thurman, R. E., Rynes, E., Humbert, R., Vierstra, J., Maurano, M. T., Haugen, E., Sheffield, N. C., Stergachis, A. B., Wang, H., Vernot, B., et al. (2012) · Nature · doi:10.1038/nature11232 · Cited by 2,679 · see citing works
Irizarry, R. A., Ladd-Acosta, C., Wen, B., Wu, Z., Montano, C., Onyango, P., Cui, H., Gabo, K., Rongione, M., Webster, M., et al. (2009) · Nature Genetics · doi:10.1038/ng.298 · Cited by 2,177 · see citing works
Transposable elements: targets for early nutritional effects on epigenetic gene regulation
Waterland, R. A., & Jirtle, R. L. (2003) · Molecular and Cellular Biology · doi:10.1128/mcb.23.15.5293-5300.2003 · Cited by 2,019 · see citing works
Doi, A., Park, I., Wen, B., Murakami, P. N., Aryee, M. J., Irizarry, R. A., Herb, B. R., Ladd‐Acosta, C., Rho, J., Loewer, S., et al. (2009) · Nature Genetics · doi:10.1038/ng.471 · Cited by 1,173 · see citing works
The clinical features, diagnosis and natural history of nonalcoholic fatty liver disease
McCullough, A. J. (2004) · Clinics in Liver Disease · doi:10.1016/j.cld.2004.04.004 · Cited by 578 · see citing works
Evaluation of the Infinium Methylation 450K technology
Dedeurwaerder, S., Defrance, M., Calonne, E., Denis, H., Sotiriou, C., & Fuks, F. (2011) · Epigenomics · doi:10.2217/epi.11.105 · Cited by 569 · see citing works
Lu, S. C., Alvarez, L., Huang, Z.-Z., Chen, L., An, W., Corrales, F. J., Avila, M. A., Kanel, G., & Mato, J. M. (2001) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.091016398 · Cited by 449 · see citing works
Liver X receptor in cholesterol metabolism
Zhao, C., & Dahlman‐Wright, K. (2009) · Journal of Endocrinology · doi:10.1677/joe-09-0271 · Cited by 418 · see citing works
Moylan, C. A., Pang, H., Dellinger, A. E., Suzuki, A., Garrett, M. E., Guy, C. D., Murphy, S. K., Ashley‐Koch, A. E., Choi, S. S., Michelotti, G. A., et al. (2013) · Hepatology · doi:10.1002/hep.26661 · Cited by 316 · see citing works
Self-citationSavard, C. E., Tartaglione, E. V., Kuver, R., Haigh, G. W., Farrell, G. C., Subramanian, S., Chait, A., Yeh, M. M., Quinn, L. S., & Ioannou, G. N. (2012) · Hepatology · doi:10.1002/hep.25789 · Cited by 297 · see citing works
Spontaneous oxidative stress and liver tumors in mice lacking methionine adenosyltransferase 1A
Martínez‐Chantar, M. L., Corrales, F. J., Martínez‐Cruz, L. A., García–Trevijano, E. R., Huang, Z., Chen, L., Kanel, G. C., Avila, M. A., Mato, J. M., & Lu, S. C.-L. (2002) · The FASEB Journal · doi:10.1096/fj.02-0078fje · Cited by 278 · see citing works
Pan-caspase inhibitor VX-166 reduces fibrosis in an animal model of nonalcoholic steatohepatitis #
Witek, R. P., Stone, C. W., Karaca, G., Syn, W., Pereira, T. A., Agboola, K. M., Omenetti, A., Jung, Y., Teaberry, V. S., Choi, S. S., et al. (2009) · Hepatology · doi:10.1002/hep.23167 · Cited by 252 · see citing works
Self-citationChanges in methionine adenosyltransferase andS-adenosylmethionine homeostasis in alcoholic rat liver
Lu, S. C.-L., Huang, Z., Yang, H., Mato, J. M., Avila, M. A., & Tsukamoto, H. (2000) · American Journal of Physiology-Gastrointestinal and Liver Physiology · doi:10.1152/ajpgi.2000.279.1.g178 · Cited by 195 · see citing works
Self-citationHypermethioninemias of genetic and non‐genetic origin: A review
Mudd, S. H. (2011) · American Journal of Medical Genetics Part C Seminars in Medical Genetics · doi:10.1002/ajmg.c.30293 · Cited by 180 · see citing works
Selçuklu, S. D., Donoghue, M. T. A., Rehmet, K., Gomes, M. D. S., Fort, A., Kovvuru, P., Muniyappa, M. K., Kerin, M. J., Enright, A. J., & Spillane, C. (2012) · Journal of Biological Chemistry · doi:10.1074/jbc.m111.335943 · Cited by 179 · see citing works
Cordero, P., Gómez-Uriz, A. M., Campión, J., Milagro, F. I., & Martínez, J. A. (2012) · Genes & Nutrition · doi:10.1007/s12263-012-0300-z · Cited by 177 · see citing works
Redefining CpG islands using hidden Markov models
Wu, H., Caffo, B. S., Jaffee, H. A., Irizarry, R. A., & Feinberg, A. P. (2010) · Biostatistics · doi:10.1093/biostatistics/kxq005 · Cited by 166 · see citing works
Caspase-1-mediated regulation of fibrogenesis in diet-induced steatohepatitis
Dixon, L. J., Berk, M. P., Thapaliya, S., Papouchado, B. G., & Feldstein, A. E. (2012) · Laboratory Investigation · doi:10.1038/labinvest.2012.45 · Cited by 159 · see citing works
Bu, S. Y., & Mashek, D. G. (2010) · Journal of Lipid Research · doi:10.1194/jlr.m009407 · Cited by 138 · see citing works
Nishida, N., Kudo, M., Nagasaka, T., Ikai, I., & Goel, A. (2012) · Hepatology · doi:10.1002/hep.25706 · Cited by 137 · see citing works
Bian, E., Huang, C. Z., Ma, T., Tao, H., Zhang, H., Chang, C. K., Lv, X., & Li, J. (2012) · Toxicology and Applied Pharmacology · doi:10.1016/j.taap.2012.06.022 · Cited by 126 · see citing works
Antifolate Drugs in Cancer Therapy
(1999) · Humana Press eBooks · doi:10.1007/978-1-59259-725-3 · Cited by 123 · see citing works
Jian, Y. U., Zhang, H. Y., Zhong, Z., Lu, W., Wang, Y., & Jingde, Z. H. U. (2003) · Cell Research · doi:10.1038/sj.cr.7290177 · Cited by 99 · see citing works
Cano, A., Buqué, X., Martinez‐Uña, M., Aurrekoetxea, I., Menor, A., García‐Rodríguez, J. L., Lu, S. C.-L., Martínez‐Chantar, M. L., Mato, J. M., Ochoa, B., et al. (2010) · Hepatology · doi:10.1002/hep.24607 · Cited by 99 · see citing works
Role of abnormal methionine metabolism in alcoholic liver injury
Lu, S. C.-L., Tsukamoto, H., & Mato, J. M. (2002) · Alcohol · doi:10.1016/s0741-8329(02)00226-4 · Cited by 96 · see citing works
Epigenetic suppression of the TGF-beta pathway revealed by transcriptome profiling in ovarian cancerPreprint
Matsumura, N., Huang, Z., Mori, S., Baba, T., Fujii, S., Konishi, I., Iversen, E. S., Berchuck, A., & Murphy, S. K. (2010) · Genome Research · doi:10.1101/gr.108803.110 · Cited by 95 · see citing works
Self-citationGlobal analysis of DNA methylation in early-stage liver fibrosis
Komatsu, Y., Waku, T., Iwasaki, N., Ono, W., Yamaguchi, C., & Yanagisawa, J. (2012) · BMC Medical Genomics · doi:10.1186/1755-8794-5-5 · Cited by 95 · see citing works
Tryndyak, V., Han, T., Muskhelishvili, L., Fuscoe, J. C., Ross, S. A., Beland, F. A., & Pogribny, I. P. (2010) · Molecular Nutrition & Food Research · doi:10.1002/mnfr.201000300 · Cited by 87 · see citing works
Frau, M., Tomasi, M. L., Simile, M. M., Demartis, M. I., Salis, F., Latte, G., Calvisi, D. F., Seddaiu, M. A., Daino, L., Feo, C. F., et al. (2012) · Hepatology · doi:10.1002/hep.25643 · Cited by 87 · see citing works
The UCSC cancer genomics browser: update 2011
Sanborn, Z., Benz, S. C., Craft, B., Szeto, C. W., Kober, K. M., Meyer, L. R., Vaske, C. J., Goldman, M. J., Smith, K. E., Kuhn, R. M., et al. (2010) · Nucleic Acids Research · doi:10.1093/nar/gkq1113 · Cited by 78 · see citing works
Christensen, K. E., & MacKenzie, R. E. (2008) · Vitamins and hormones · doi:10.1016/s0083-6729(08)00414-7 · Cited by 73 · see citing works
Epigenetic Silencing of ALDH1L1, a Metabolic Regulator of Cellular Proliferation, in Cancers
Oleinik, N. V., Krupenko, N. I., & Krupenko, S. A. (2011) · Genes & Cancer · doi:10.1177/1947601911405841 · Cited by 60 · see citing works
Noninvasive diagnosis of nonalcoholic fatty liver disease
Myers, R. P. (2009) · Annals of Hepatology · doi:10.1016/s1665-2681(19)31823-x · Cited by 59 · see citing works
Quantitative promoter methylation analysis of hepatocellular carcinoma, cirrhotic and normal liver
Harder, J., Opitz, O. G., Brabender, J., Olschewski, M., Blum, H. E., Nomoto, S., & Usadel, H. (2008) · International Journal of Cancer · doi:10.1002/ijc.23433 · Cited by 58 · see citing works
DNA Methylation Profiles of Organic Anion Transporting Polypeptide 1B3 in Cancer Cell Lines
Ichihara, S., Kikuchi, R., Kusuhara, H., Imai, S., Maeda, K., & Sugiyama, Y. (2010) · Pharmaceutical Research · doi:10.1007/s11095-010-0064-3 · Cited by 44 · see citing works
Analysis of DNA Methylation and Histone Modification Profiles of Liver-Specific Transporters
Imai, S., Kikuchi, R., Kusuhara, H., Yagi, S., Shiota, K., & Sugiyama, Y. (2008) · Molecular Pharmacology · doi:10.1124/mol.108.052589 · Cited by 42 · see citing works
Decreased expression of ALDH1L1 is associated with a poor prognosis in hepatocellular carcinoma
Chen, X.-Q., He, J.-R., & Wang, H. (2011) · Medical Oncology · doi:10.1007/s12032-011-0075-x · Cited by 40 · see citing works
Shimizu, H., Horii, A., Sunamura, M., Motoi, F., Egawa, S., Unno, M., & Fukushige, S. (2011) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2011.06.121 · Cited by 39 · see citing works
Systems Biology for Signaling Networks
Choi, S. (2010) · Systems biology · doi:10.1007/978-1-4419-5797-9 · Cited by 37 · see citing works
Inhibition of human methionine adenosyltransferase 1A transcription by coding region methylation
Tomasi, M. L., Li, T. W. H., Li, M., Mato, J. M., & Lu, S. C.-L. (2011) · Journal of Cellular Physiology · doi:10.1002/jcp.22875 · Cited by 36 · see citing works
Folate Biochemistry in Relation to Antifolate Selectivity
Kisliuk, R. L. (1999) · Humana Press eBooks · doi:10.1007/978-1-59259-725-3_2 · Cited by 29 · see citing works
A novel four transmembrane spanning protein, CLP24
Kearsey, J., Petit, S., Oliveira, C. D., & Schweighoffer, F. (2004) · European Journal of Biochemistry · doi:10.1111/j.1432-1033.2004.04186.x · Cited by 24 · see citing works
Russmann, S., Junker, E., & Lauterburg, B. H. (2002) · Hepatology · doi:10.1053/jhep.2002.36499 · Cited by 20 · see citing works
Expression of tumor-associated aldehyde dehydrogenase gene in rat hepatoma cell lines.
Lin, K., Brennan, M. D., & Lindahl, R. G. (1988) · PubMed · Cited by 17 · see citing works
Pathogenesis of Obesity-Related Chronic Liver Diseases as the Study Case for the Systems Biology
Baranova, A. V., Birerdinc, A., Estep, M., & Younossi, Z. M. (2010) · Systems biology · doi:10.1007/978-1-4419-5797-9_26 · Cited by 2 · see citing works
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- [10]Moylan CA Pang H Dellinger A Hepatic gene expression profiles differentiate pre-symptomatic NAFLD patients with high versus low risk for liver related mortality Hepatology 2013 in press
Cited by
Sorted by citations
MAFLD: a consensus-driven proposed nomenclature for metabolic associated fatty liver disease
Eslam, M., Sanyal, A. J., George, J., Sanyal, A., Neuschwander-Tetri, B., Tiribelli, C., Kleiner, D. E., Brunt, E., Bugianesi, E., Yki-Järvinen, H., et al. (2020) · Gastroenterology · doi:10.1053/j.gastro.2019.11.312 · Cited by 3,286 · see citing works
Self-citationBoursier, J., Mueller, O., Barret, M., Machado, M., Fizanne, L., Araujo‐Perez, F., Guy, C. D., Seed, P. C., Rawls, J. F., David, L. A., et al. (2016) · Hepatology · doi:10.1002/hep.28356 · Cited by 1,483 · see citing works
“Several other factors that influence the course of the disease have been identified, such as epigenetics,((4)) hormonal status,((5)) or nutrition.”
BackgroundSelf-citationTriggering and resolution of inflammation in NASH
Schuster, S., Cabrera, D., Arrese, M., & Feldstein, A. E. (2018) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/s41575-018-0009-6 · Cited by 943 · see citing works
Nonalcoholic fatty liver disease
Brunt, E., Wong, V., Nobili, V., Day, C., Sookoian, S., Maher, J., Bugianesi, E., Sirlin, C., Neuschwander-Tetri, B., & Rinella, M. (2015) · Nature Reviews Disease Primers · doi:10.1038/nrdp.2015.80 · Cited by 591 · see citing works
Genetics and epigenetics of NAFLD and NASH: Clinical impact
Eslam, M., Valenti, L., & Romeo, S. (2018) · Journal of Hepatology · doi:10.1016/j.jhep.2017.09.003 · Cited by 971 · see citing works
Nonalcoholic Fatty Liver Disease: Pathogenesis and Disease Spectrum
Hardy, T., Oakley, F., Anstee, Q. M., & Day, C. P. (2016) · Annual Review of Pathology Mechanisms of Disease · doi:10.1146/annurev-pathol-012615-044224 · Cited by 619 · see citing works
“methylation in mild (F1-2) versus severe (F3-4) NAFLD of genes that were hypomethylated and thus overexpressed in advanced NAFLD (275).”
BackgroundPathophysiology and Mechanisms of Nonalcoholic Fatty Liver Disease.
Haas, J., Francque, S., & Staels, B. (2016) · Annual Review of Physiology · doi:10.1146/annurev-physiol-021115-105331 · Cited by 372 · see citing works
Machado, M. V., Michelotti, G. A., Xie, G., Pereira, T. A., Boursier, J., Bohnic, B., Guy, C. D., & Diehl, A. M. (2015) · PLoS ONE · doi:10.1371/journal.pone.0127991 · Cited by 381 · see citing works
Self-citationNAFLD in children: new genes, new diagnostic modalities and new drugs
Nobili, V., Alisi, A., Valenti, L. V. C., Miele, L., Feldstein, A. E., & Alkhouri, N. (2019) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/s41575-019-0169-z · Cited by 311 · see citing works
Non-Alcoholic Fatty Liver Disease: Metabolic, Genetic, Epigenetic and Environmental Risk Factors
Juanola, O., Martínez‐López, S., Francés, R., & Gómez‐Hurtado, I. (2021) · International Journal of Environmental Research and Public Health · doi:10.3390/ijerph18105227 · Cited by 303 · see citing works
“NAFLD has mainly been associated with hypomethylation [173], most probably caused by an imbalance in methyl donor supply (reduced levels of folate) as has been suggested for T2DM [174].”
BackgroundMetabolomic identification of subtypes of nonalcoholic steatohepatitis
Alonso, C., Fernández-Ramos, D., Varela-Rey, M., Martínez-Arranz, I., Navasa, N., Van Liempd, S. M., Lavín Trueba, J. L., Mayo, R., Ilisso, C. P., de Juan, V. G., et al. (2017) · Gastroenterology · doi:10.1053/j.gastro.2017.01.015 · Cited by 263 · see citing works
Endocrine-disrupting chemicals and fatty liver disease
Foulds, C., Treviño, L., York, B., & Walker, C. (2017) · Nature Reviews Endocrinology · doi:10.1038/nrendo.2017.42 · Cited by 217 · see citing works
Genetic predisposition in nonalcoholic fatty liver disease
Sookoian, S. C., & Pirola, C. J. (2017) · Clinical and Molecular Hepatology · doi:10.3350/cmh.2016.0109 · Cited by 215 · see citing works
Papatheodoridi, A., Chrysavgis, L., Koutsilieris, M., & Chatzigeorgiou, A. (2019) · Hepatology · doi:10.1002/hep.30834 · Cited by 206 · see citing works
“(38) These results indicate that proteins involved in senescence are overexpressed in NAFLD.”
BackgroundInfluentialUrea cycle dysregulation in non-alcoholic fatty liver disease
Chiara, F. D., Heebøll, S., Marrone, G., Montoliu, C., Hamilton-Dutoit, S. J., Ferrandez, A., Andreola, F., Rombouts, K., Grønbæk, H., Felipo, V., et al. (2018) · Journal of Hepatology · doi:10.1016/j.jhep.2018.06.023 · Cited by 207 · see citing works
“Furthermore, patients with NAFLD have been shown to have hyperammonemia and neuropsychological disturbances (17), although the mechanism underlying this has so far not been clarified.”
BackgroundInfluentialNon-alcoholic fatty liver disease: What the clinician needs to know
Machado, M. V. (2014) · World Journal of Gastroenterology · doi:10.3748/wjg.v20.i36.12956 · Cited by 209 · see citing works
Nonalcoholic fatty liver disease: Evolving paradigms
Lonardo, A., Nascimbeni, F., Maurantonio, M., Marrazzo, A., Rinaldi, L., & Adinolfi, L. E. (2017) · World Journal of Gastroenterology · doi:10.3748/wjg.v23.i36.6571 · Cited by 197 · see citing works
Akkız, H., Gieseler, R. K., & Canbay, A. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms25147873 · Cited by 191 · see citing works
“A genome-wide study of DNA methylation patterns in CCl 4 mouse liver tissues revealed the hypomethylation of fibrosis-related genes before the onset of liver fibrosis [170].”
BackgroundEtiology of Hepatocellular Carcinoma: Special Focus on Fatty Liver Disease
Suresh, D., Srinivas, A. N., & Kumar, D. P. (2020) · Frontiers in Oncology · doi:10.3389/fonc.2020.601710 · Cited by 173 · see citing works
“Studies carried out in mouse models of NAFLD and also in patients with NAFLD or HCC have identified epigenetic-mediated gene regulation involved in the development and progression of the disease (80, 81).”
BackgroundZeybel, M., Hardy, T., Robinson, S. M., Fox, C., Anstee, Q. M., Ness, T., Masson, S., Mathers, J. C., French, J., White, S., et al. (2015) · Clinical Epigenetics · doi:10.1186/s13148-015-0056-6 · Cited by 180 · see citing works
“Although DNA methylation analysis has not been used to predict liver injury outcome, there have been several studies indicating that changes in locus-specific DNA methylation can affect insulin resistance and severity of non-alcoholic fatty liver disease (NAFLD), as well as predict the response to a low-calorie diet […”
BackgroundResultEpigenetics in liver disease: from biology to therapeutics
Hardy, T., & Mann, D. A. (2016) · Gut · doi:10.1136/gutjnl-2015-311292 · Cited by 177 · see citing works
“88 The majority of differentially methylated sites became hypomethylated with disease progression (76%), whereas 24% underwent hypermethylation.”
BackgroundPerakakis, N., Stefanakis, K., & Mantzoros, C. S. (2020) · Metabolism · doi:10.1016/j.metabol.2020.154320 · Cited by 163 · see citing works
“Through global microarray transcriptional snapshots, NAFLD and especially NASH are characterized by overexpression of genes associated with lipid metabolism [89–92], acute phase regulators of insulin sensitivity [93], cellular division [89], DNA [89] and tissue repair [56], extracellular matrix organization [91,94–96]…”
Found in translation—Fibrosis in metabolic dysfunction–associated steatohepatitis (MASH)
Wang, S., & Friedman, S. L. (2023) · Science Translational Medicine · doi:10.1126/scitranslmed.adi0759 · Cited by 158 · see citing works
“…as those encoding TGFβ1, COL1A1, PDGFα, peroxisome pro-liferator – activated receptor alpha (PPARα), and peroxisome proliferator – activated receptor delta (PPARδ), can not only distinguish between patients with mild versus advanced MASLD but also predict future fibrosis progression ( 168 – 171 ).”
BackgroundGenetic and epigenetic factors determining NAFLD risk
Jonas, W., & Schürmann, A. (2020) · Molecular Metabolism · doi:10.1016/j.molmet.2020.101111 · Cited by 157 · see citing works
“suggested that the data might help to establish non-invasive markers to identify NAFLD patients at a high risk of liver disease progression [100].”
BackgroundMethodMann, D. A. (2014) · Hepatology · doi:10.1002/hep.27131 · Cited by 153 · see citing works
Genetic and Epigenetic Regulation in Nonalcoholic Fatty Liver Disease (NAFLD)
Campo, J. A. D., Gallego‐Durán, R., Gallego, P., & Grande, L. (2018) · International Journal of Molecular Sciences · doi:10.3390/ijms19030911 · Cited by 146 · see citing works
“Differential methylation may contribute to significant differences in gene expression; 69,247 CpG sites with a different methylation pattern (78% hypomethylated, 24% hypermethylated) have been described in liver tissue of 100 patients with different stages of disease [59,60].”
BackgroundBarbier‐Torres, L., Fortner, K. A., Iruzubieta, P., Delgado, T. C., Giddings, E. L., Chen, Y., Champagne, D., Fernández‐Ramos, D., Mestre, D., Gómez‐Santos, B., et al. (2020) · Nature Communications · doi:10.1038/s41467-020-16991-2 · Cited by 142 · see citing works
Epigenetics in NAFLD/NASH: Targets and therapy
Sodum, N., Kumar, G., Bojja, S. L., Kumar, N., & Rao, C. M. (2021) · Pharmacological Research · doi:10.1016/j.phrs.2021.105484 · Cited by 145 · see citing works
Kirchner, H., Sinha, I., Gao, H., Ruby, M. A., Schönke, M., Lindvall, J. M., Barrès, R., Krook, A., Näslund, E., Dahlman-Wright, K., et al. (2016) · Molecular Metabolism · doi:10.1016/j.molmet.2015.12.004 · Cited by 125 · see citing works
“This is an www.molecularmetabolism.com Activation of PRKCε is implicated in hepatic insulin resistance in NAFLD [1,21,25].”
BackgroundResultInfluentialEpigenetics and Liver Fibrosis
Morán‐Salvador, E., & Mann, J. (2017) · Cellular and Molecular Gastroenterology and Hepatology · doi:10.1016/j.jcmgh.2017.04.007 · Cited by 137 · see citing works
“8 The interrogation of DNA methylome signatures in hu man liver can distinguish patients with different stages of NAFLD or fibrosis [56-58].”
BackgroundPathogenesis of NASH: the Impact of Multiple Pathways
Noureddin, M., & Sanyal, A. J. (2018) · Current Hepatology Reports · doi:10.1007/s11901-018-0425-7 · Cited by 135 · see citing works
TGFβ2 and TGFβ3 isoforms drive fibrotic disease pathogenesis
Sun, T., Huang, Z., Liang, W.-C., Yin, J., Lin, W. Y., Wu, J., Vernes, J.-M., Lutman, J., Caplazi, P., Jeet, S., et al. (2021) · Science Translational Medicine · doi:10.1126/scitranslmed.abe0407 · Cited by 134 · see citing works
Tian, Y., Wong, V. W., Wong, G. L., Yang, W., Sun, H., Shen, J., TONG, J. H. M., Go, M. Y. Y., Cheung, Y. S., Lai, P. B. S., et al. (2015) · Cancer Research · doi:10.1158/0008-5472.can-14-3786 · Cited by 134 · see citing works
“6 altered DNA methylation may contribute to the progression of NAFLD (13,14), the role of”
Page, A., Paoli, P. P., Salvador, E. M., White, S. A., French, J., & Mann, J. (2015) · Journal of Hepatology · doi:10.1016/j.jhep.2015.11.024 · Cited by 131 · see citing works
Ke, Z.-H., Pan, J., Jin, L., Xu, H., Yu, T., Ullah, K., Rahman, T. U., Ren, J. T., Cheng, Y., Dong, X., et al. (2016) · Scientific Reports · doi:10.1038/srep31331 · Cited by 133 · see citing works
Epigenetics in non-alcoholic fatty liver disease
Lee, J.-H., Kim, Y., Friso, S., & Choi, S. (2016) · Molecular Aspects of Medicine · doi:10.1016/j.mam.2016.11.008 · Cited by 134 · see citing works
Komatsu, M., Kanda, T., Urai, H., Kurokochi, A., Kitahama, R., Shigaki, S., Ono, T., Yukioka, H., Hasegawa, K., Tokuyama, H., et al. (2018) · Scientific Reports · doi:10.1038/s41598-018-26882-8 · Cited by 126 · see citing works
Nutrition and Genetics in NAFLD: The Perfect Binomium
Meroni, M., Longo, M., Rustichelli, A., & Dongiovanni, P. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21082986 · Cited by 122 · see citing works
“Among these genes, altered methylation of Fibroblast growth factor receptor 2 (FGFR2) and Caspase 1 (CASP1), which are involved in epithelial to mesenchymal transition, inflammation and fibrotic processes, seemed to play a crucial role in the progression to cirrhosis and HCC [104].”
BackgroundMolecular signatures of long-term hepatocellular carcinoma risk in nonalcoholic fatty liver disease
Fujiwara, N., Kubota, N., Crouchet, É., Koneru, B., Marquez, C. A., Jajoriya, A. K., Panda, G., Qian, T., Zhu, S., Goossens, N., et al. (2022) · Science Translational Medicine · doi:10.1126/scitranslmed.abo4474 · Cited by 124 · see citing works
Pastore, A., Alisi, A., Giovamberardino, G. D., Crudele, A., Ceccarelli, S., Panera, N., Dionisi‐Vici, C., & Nobili, V. (2014) · International Journal of Molecular Sciences · doi:10.3390/ijms151121202 · Cited by 122 · see citing works
“found that human livers with advanced NAFLD are generally hypomethylated relative to those with mild NAFLD [34].”
BackgroundBiopsy and Noninvasive Methods to Assess Progression of Nonalcoholic Fatty Liver Disease
Bédossa, P., & Patel, K. (2016) · Gastroenterology · doi:10.1053/j.gastro.2016.03.008 · Cited by 122 · see citing works
Epigenetic Mechanisms Underlying the Link between Non-Alcoholic Fatty Liver Diseases and Nutrition
Lee, J. Y., Friso, S., & Choi, S. (2014) · Nutrients · doi:10.3390/nu6083303 · Cited by 121 · see citing works
“A recent methylome and transcriptome study found that differentially methylated genes may distinguish patients with advanced NASH from simple steatosis [55].”
BackgroundLefebvre, P., Lalloyer, F., Baugé, E., Pawlak, M., Gheeraert, C., Dehondt, H., Vanhoutte, J., Woitrain, E., Hennuyer, N., Mazuy, C., et al. (2017) · JCI Insight · doi:10.1172/jci.insight.92264 · Cited by 117 · see citing works
“Comparing the liver transcriptome of NAFLD patients with no or little fibrosis to the one of fibrotic patients revealed genes involved in cellular proliferation and ECM organization (27, 28).”
BackgroundGenetic Basis of Drug-Induced Liver Injury: Present and Future
Urban, T. J., Aithal, G. P., & Daly, A. K. (2014) · Seminars in Liver Disease · doi:10.1055/s-0034-1375954 · Cited by 109 · see citing works
Noureddin, M., Mato, J. M., & Lu, S. C.-L. (2015) · Experimental Biology and Medicine · doi:10.1177/1535370215579161 · Cited by 109 · see citing works
“In another human study, VLDL hepatic secretion was lower in NASH patients compared to simple steatosis, which was attributed to a greater decrease in PC.103 Another group has shown that the hepatic PC–PE ratio was significantly lower in NASH patients compared to healthy controls.70 An important study has found that a…”
BackgroundInfluentialEpigenetic regulation of hepatocellular carcinoma in non-alcoholic fatty liver disease
Tian, Y., Wong, V. W., Chan, H. L., & Cheng, A. S. L. (2013) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2013.08.010 · Cited by 107 · see citing works
Palma, R., Pronio, A., Romeo, M., Scognamiglio, F., Ventriglia, L., Ormando, V. M., Lamazza, A., Pontone, S., Federico, A., & Dallio, M. (2022) · Journal of Clinical Medicine · doi:10.3390/jcm11133649 · Cited by 111 · see citing works
“DNA hypomethylation ↑ FGFR2 Pro-fibrogenic [96] ↑ PGC1a, ↑ SREBF2, ↑ FOXA1, ↑ FOXA2 Hepatic regulators of glucose and lipid metabolism [97]”
BackgroundInfluentialPotential Epigenetic Mechanism in Non-Alcoholic Fatty Liver Disease
Sun, C., Fan, J., & Qiao, L. (2015) · International Journal of Molecular Sciences · doi:10.3390/ijms16035161 · Cited by 106 · see citing works
“Murphy and colleagues have found 69,247 methylated CpG sites in NAFLD patients [59].”
BackgroundXiong, L., Wu, F., Wu, Q., Xu, L., Cheung, O. K.-W., Kang, W., Mok, M. T. S., Szeto, L. L. M., Lun, C.-Y., Lung, R. W. M., et al. (2019) · Nature Communications · doi:10.1038/s41467-018-08245-z · Cited by 105 · see citing works
Abderrahmani, A., Yengo, L., Caiazzo, R. J., Canouil, M., Cauchi, S., Raverdy, V., Plaisance, V., Pawlowski, V., Lobbens, S., Maillet, J., et al. (2018) · Diabetes · doi:10.2337/db17-1539 · Cited by 100 · see citing works
“Therefore, in the liver of obese patients with T2D, the increased PDGF-AA signaling contributes to insulin resistance, opening new therapeutic avenues against T2D and possibly NAFLD.”
BackgroundResultInfluentialDNA Methylation in Nonalcoholic Fatty Liver Disease
Hyun, J., & Jung, Y. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21218138 · Cited by 99 · see citing works
“FGFR2 (cg01385327), CASP1 (cg13802966), MAT1A (cg19423196) FGFR2, CASP1: hypo; MAT1A: hyper Frozen liver biopsy Liver fibrosis 25 controls, 90 NAFLD (52 mild and 38 severe fibrosis) Infinium HumanMethylation450 BeadChip, bisulfite pyrosequencing 2013 [114]”
MethodStevanović, J., Beleza, J., Coxito, P. M., Ascensão, A. A. M. R., & Magalhães, J. (2019) · Molecular Metabolism · doi:10.1016/j.molmet.2019.11.015 · Cited by 96 · see citing works
“Some studies propose DNA methylation status as a marker of progression of NAFLD [151,152], however, this field remains quite open for research regarding NAFLD treatment through changes in lifestyle.”
BackgroundPathophysiological underpinnings of metabolic dysfunction-associated steatotic liver disease
Kuchay, M. S., Choudhary, N. S., & Ramos‐Molina, B. (2025) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.00951.2024 · Cited by 97 · see citing works
Epigenetics in idiopathic pulmonary fibrosis
Tzouvelekis, A., & Kaminski, N. (2015) · Biochemistry and Cell Biology · doi:10.1139/bcb-2014-0126 · Cited by 88 · see citing works
The Importance of Patient-Specific Factors for Hepatic Drug Response and Toxicity
Lauschke, V. M., & Ingelman‐Sundberg, M. (2016) · International Journal of Molecular Sciences · doi:10.3390/ijms17101714 · Cited by 90 · see citing works
Methionine adenosyltransferases in cancers: Mechanisms of dysregulation and implications for therapy
Maldonado, L. Y., Arsene, D., Mato, J. M., & Lu, S. C.-L. (2017) · Experimental Biology and Medicine · doi:10.1177/1535370217740860 · Cited by 88 · see citing works
Epigenetic Modifications in the Biology of Nonalcoholic Fatty Liver Disease
Pirola, C. J., Scian, R., Gianotti, T. F., Dopazo, H., Rohr, C., Martino, J. S., Castaño, G. O., & Sookoian, S. C. (2015) · Medicine · doi:10.1097/md.0000000000001480 · Cited by 88 · see citing works
Jueliger, S., Lyons, J. F., Cannito, S., Pata, I., Pata, P., Školnaja, M., Re, O. L., Peyrou, M., Villarroya, F., Pazienza, V., et al. (2016) · Epigenetics · doi:10.1080/15592294.2016.1214781 · Cited by 87 · see citing works
del Río-Moreno, M., Alors‐Pérez, E., González‐Rubio, S., Ferrín, G., Reyes, Ó., Rodríguez‐Perálvarez, M., Sánchez‐Frías, M., Sánchez‐Sánchez, R., Ventura, S., López‐Miranda, J., et al. (2019) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2019-00021 · Cited by 84 · see citing works
Nikolaou, N., Gathercole, L., Marchand, L., Althari, S., Dempster, N. J., Green, C., van de Bunt, M., McNeil, C. A., Arvaniti, A., Hughes, B. A., et al. (2019) · Metabolism · doi:10.1016/j.metabol.2019.153947 · Cited by 87 · see citing works
Kitamoto, T., Kitamoto, A., Ogawa, Y., Honda, Y., Imajo, K., Saito, S., Yoneda, M., Nakamura, T., Nakajima, A., & Hotta, K. (2015) · Journal of Hepatology · doi:10.1016/j.jhep.2015.02.049 · Cited by 83 · see citing works
“These findings are consistent with our data reported here, and the database [18] indicates further that methylation of CpG99 does not differ between patients with mild or advanced NAFLD [18].”
BackgroundResultInfluentialMethionine adenosyltransferases in liver cancer
Murray, B., Barbier‐Torres, L., Fan, W., Mato, J. M., & Lu, S. C.-L. (2019) · World Journal of Gastroenterology · doi:10.3748/wjg.v25.i31.4300 · Cited by 82 · see citing works
Kim, Y.-C., Seok, S., Zhang, Y., Ma, J., Kong, B., Guo, G. L., Kemper, B., & Kemper, J. (2020) · Nature Communications · doi:10.1038/s41467-020-19803-9 · Cited by 73 · see citing works
DNA methylation signatures reflect aging in patients with nonalcoholic steatohepatitis
Loomba, R. S., Gindin, Y., Jiang, Z., Lawitz, E., Caldwell, S. H., Djedjos, C. S., Xu, R., Chung, C., Myers, R. P., Subramanian, G. M., et al. (2018) · JCI Insight · doi:10.1172/jci.insight.96685 · Cited by 79 · see citing works
“The hierarchical model of NAFLD: Prognostic significance of histologic features in NASH.”
BackgroundInfluentialSelf-citationMartinou, E., Pericleous, M., Stefanova, I., Kaur, V., & Angelidi, A. M. (2022) · Diagnostics · doi:10.3390/diagnostics12020407 · Cited by 76 · see citing works
Evaluating causality of cellular senescence in non-alcoholic fatty liver disease
Meijnikman, A. S., Herrema, H., Scheithauer, T. P. M., Kroon, J., Nieuwdorp, M., & Groen, A. K. (2021) · JHEP Reports · doi:10.1016/j.jhepr.2021.100301 · Cited by 77 · see citing works
“distinguished from individualswithNAFLDwith advancedfibrosis based on different methylation patterns.(128) Individuals with advanced fibrosis had more hypomethylated genes in their liver”
BackgroundSzukiewicz, D., Trojanowski, S., Kociszewska, A., & Szewczyk, G. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms232314663 · Cited by 79 · see citing works
The Role of the Transsulfuration Pathway in Non-Alcoholic Fatty Liver Disease
Werge, M. P., McCann, A., Galsgaard, E. D., Holst, D., Bugge, A. K., Albrechtsen, N. J. W., & Gluud, L. L. (2021) · Journal of Clinical Medicine · doi:10.3390/jcm10051081 · Cited by 75 · see citing works
Zubiete‐Franco, I., García‐Rodríguez, J. L., Martinez‐Uña, M., Martínez-López, N., Woodhoo, A., de Juan, V. G., Beraza, N., Lage, S., Andrade, F., Llarena, M., et al. (2015) · Journal of Hepatology · doi:10.1016/j.jhep.2015.08.037 · Cited by 73 · see citing works
“Recently, it was shown that GNMT mRNA levels were often repressed in advanced NAFLD patients[12].”
BackgroundInfluentialTaghdouini, A. E., Sørensen, A. L., Reiner, A. H., Coll, M., Verhulst, S., Mannaerts, I., Øie, C. I., Smedsrød, B. H., Najimi, M., Sokal, E. M., et al. (2015) · Oncotarget · doi:10.18632/oncotarget.4925 · Cited by 72 · see citing works
Nishida, N., Yada, N., Hagiwara, S., Sakurai, T., Kitano, M., & Kudo, M. (2016) · Journal of Gastroenterology and Hepatology · doi:10.1111/jgh.13318 · Cited by 72 · see citing works
Epigenetic Mechanisms in Hepatic Stellate Cell Activation During Liver Fibrosis and Carcinogenesis
Bárcena‐Varela, M., Colyn, L., & Fernández‐Barrena, M. G. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20102507 · Cited by 72 · see citing works
“They found that DNA methylation status at specific CpGs might be useful for predicting progression of the disease and development of fibrosis, further supporting their previous studies on DNA methylome signatures and NAFLD patient’s stratification [83].”
ResultGenetics of Nonalcoholic Fatty Liver Disease: From Pathogenesis to Therapeutics
Sookoian, S. C., & Pirola, C. J. (2019) · Seminars in Liver Disease · doi:10.1055/s-0039-1679920 · Cited by 70 · see citing works
Human liver epigenetic alterations in non-alcoholic steatohepatitis are related to insulin action
de Mello, V. D., Matte, A., Perfilyev, A., Männistö, V., Rönn, T., Nilsson, E., Käkelä, P., Ling, C., & Pihlajamäki, J. (2017) · Epigenetics · doi:10.1080/15592294.2017.1294305 · Cited by 70 · see citing works
“We further tested if epigenetic changes in the liver were associated with clinical phenotypes that are related to NAFLD.”
BackgroundResultInfluentialFujiwara, N., Kobayashi, M., Fobar, A. J., Hoshida, A., Marquez, C. A., Koneru, B., Panda, G., Taguri, M., Qian, T., Raman, I., et al. (2021) · Med · doi:10.1016/j.medj.2021.03.017 · Cited by 70 · see citing works
Nonalcoholic steatohepatitis is associated with a state of betaine‐insufficiency
Sookoian, S., Puri, P., Castaño, G. O., Scian, R., Mirshahi, F., Sanyal, A. J., & Pirola, C. J. (2016) · Liver International · doi:10.1111/liv.13249 · Cited by 68 · see citing works
Genetic and epigenetic mechanisms of NASH
Eslam, M., & George, J. (2015) · Hepatology International · doi:10.1007/s12072-015-9689-y · Cited by 67 · see citing works
“[84] Genome-wide methylation profiles Mild disease (F0–F1) versus advanced NAFLD (F3–F4) 56 NAFLD patients in the discovery cohort and 34 in the replication cohort”
BackgroundWnt signaling in liver regeneration, disease, and cancer
Zou, G., & Park, J.-I. (2023) · Clinical and Molecular Hepatology · doi:10.3350/cmh.2022.0058 · Cited by 64 · see citing works
Jia, X., & Zhai, T. (2019) · Frontiers in Endocrinology · doi:10.3389/fendo.2019.00599 · Cited by 63 · see citing works
“Identifying gene-specific expression patterns has been useful in the understanding of pathogenic mechanisms or therapeutic assessment for multiple diseases, NAFLD included (6, 7).”
Backgroundp53 as a Dichotomous Regulator of Liver Disease: The Dose Makes the Medicine
Krstić, J., Galhuber, M., Schulz, T. J., Schupp, M., & Prokesch, A. (2018) · International Journal of Molecular Sciences · doi:10.3390/ijms19030921 · Cited by 63 · see citing works
“Besides genetic [6] and epigenetic (mostly differential DNA methylation [7]) aberrations, infection with hepatitis B and C virus and aflatoxin B1 exposure were historically prevalent risk factors for liver disease development.”
BackgroundLiang, N., Damdimopoulos, A., Goñi, S., Huang, Z.-Q., Vedin, L.-L., Jakobsson, T., Giudici, M., Ahmed, O., Pedrelli, M., Barilla, S., et al. (2019) · Nature Communications · doi:10.1038/s41467-019-09524-z · Cited by 56 · see citing works
Methionine adenosyltransferases in liver health and diseases
Ramani, K., & Lu, S. C.-L. (2017) · Liver Research · doi:10.1016/j.livres.2017.07.002 · Cited by 62 · see citing works
Mitochondrial role in the neonatal predisposition to developing nonalcoholic fatty liver disease
Baker, P. R., & Friedman, J. E. (2018) · Journal of Clinical Investigation · doi:10.1172/jci120846 · Cited by 61 · see citing works
Lai, Z., Chen, J., Ding, C., Wong, K., Chen, X., Pu, L., Huang, Q., Chen, X., Cheng, Z., Liu, Y., et al. (2019) · Obesity · doi:10.1002/oby.22667 · Cited by 61 · see citing works
“For example, the DNA methylation levels of antifibrogenic genes (peroxisome proliferator activated receptor [PPAR] α, γ, and δ) in the liver were found to increase with hepatic fibrosis severity in patients with NAFLD and alcoholic fatty liver disease (4-6).”
BackgroundNAFLD-Associated HCC: Progress and Opportunities
Geh, D., Anstee, Q. M., & Reeves, H. L. (2021) · Journal of Hepatocellular Carcinoma · doi:10.2147/jhc.s272213 · Cited by 61 · see citing works
“74,75 Importantly the methylation of circulating cell-free DNA (cfDNA) can be analysed.”
Jurado‐Ruiz, E., Varela, L. M., Luque‐Sierra, A., Berná, G., Cahuana, G. M., Martínez‐Force, E., Gallego‐Durán, R., Soria, B., de Roos, B., Romero‐Gómez, M., et al. (2016) · Molecular Nutrition & Food Research · doi:10.1002/mnfr.201600549 · Cited by 60 · see citing works
“Additionally, livers with advanced NAFLD show increased expression of hypomethylated genes relative to that in livers with mild NAFLD [35], and hypomethylation is very important for the progression of liver fibrosis in the early stages of the disease [36].”
BackgroundHotta, K., Kitamoto, A., Kitamoto, T., Ogawa, Y., Honda, Y., Kessoku, T., Yoneda, M., Imajo, K., Tomeno, W., Saito, S., et al. (2018) · Scientific Reports · doi:10.1038/s41598-018-31886-5 · Cited by 60 · see citing works
Epigenetics of Hepatic Insulin Resistance
Maude, H., Sanchez-Cabanillas, C., & Cebola, I. (2021) · Frontiers in Endocrinology · doi:10.3389/fendo.2021.681356 · Cited by 60 · see citing works
“In it perhaps not entirely unexpected that the methylation of FGFR2 was found markedly altered in advanced NAFLD, with 23 CpG sites hypomethylated, promoting its overexpression and the establishment of an inflammatory and pro-fibrotic niche (75).”
BackgroundEpigenetic Regulation of Hepatic Lipid Metabolism by DNA Methylation
Wang, S., Zha, L., Cui, X., Yeh, Y., Liu, R., Jing, J., Shi, H., Chen, W., Hanover, J. A., Yin, J., et al. (2023) · Advanced Science · doi:10.1002/advs.202206068 · Cited by 59 · see citing works
Hotta, K., Kitamoto, T., Kitamoto, A., Ogawa, Y., Honda, Y., Kessoku, T., Yoneda, M., Imajo, K., Tomeno, W., Saito, S., et al. (2017) · Hepatology Research · doi:10.1111/hepr.12992 · Cited by 59 · see citing works
Campisano, S., la Colla, A. B., Echarte, S. M., & Chisari, A. N. (2019) · Nutrition Research Reviews · doi:10.1017/s0954422418000239 · Cited by 59 · see citing works
“Furthermore, nearly 70 000 methylated CpG sites in genes related to tissue repair and metabolic regulation have been found in these patients((55)).”
BackgroundCellular Senescence in Liver Disease and Regeneration
Ferreira-González, S., Rodrigo‐Torres, D., Gadd, V. L., & Forbes, S. J. (2021) · Seminars in Liver Disease · doi:10.1055/s-0040-1722262 · Cited by 58 · see citing works
Ma, J., Nano, J., Ding, J., Zheng, Y., Hennein, R., Liu, C., Speliotes, E. K., Huan, T., Song, C., Mendelson, M., et al. (2019) · Diabetes · doi:10.2337/db18-1193 · Cited by 59 · see citing works
“Previous studies using array-based methods have examined epigenome-wide DNA methylation patterns in liver samples of individuals with biopsy-proven NAFLD (5,6).”
BackgroundMartinez‐Uña, M., Varela‐Rey, M., Mestre, D., Fernández-Ares, L., Fresnedo, O., Fernández‐Ramos, D., Juan, V. G., Martín‐Guerrero, I., García‐Orad, Á., Luka, Z., et al. (2014) · Journal of Hepatology · doi:10.1016/j.jhep.2014.10.019 · Cited by 58 · see citing works
“It has recently been described [25,26] that”
DNA methylation markers in the detection of hepatocellular carcinoma
Fu, S., Debes, J. D., & Boonstra, A. (2023) · European Journal of Cancer · doi:10.1016/j.ejca.2023.112960 · Cited by 56 · see citing works
Epigenetic Activation of Wnt/β-Catenin Signaling in NAFLD-Associated Hepatocarcinogenesis
Tian, Y., Mok, M. T. S., Yang, P., & Cheng, A. S. L. (2016) · Cancers · doi:10.3390/cancers8080076 · Cited by 55 · see citing works
“These findings support that epigenetic dysregulation is associated with NAFLD progression and HCC initiation [46].”
BackgroundResultKim, H.-J., Worsley, O., Yang, E., Purbojati, R. W., Liang, A. L., Tan, W. L. W., Moses, D., Hartono, S., Fan, V. S. K., Lim, T. K. H., et al. (2019) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-019-03114-4 · Cited by 54 · see citing works
Epigenetic Biomarkers for the Diagnosis and Treatment of Liver Disease
Arechederra, M., Recalde, M., Gárate‐Rascón, M., Fernández‐Barrena, M. G., Avila, M. A., & Berasain, C. (2021) · Cancers · doi:10.3390/cancers13061265 · Cited by 53 · see citing works
“NAFLD/NASH Differentially methylated CpG sigantures [53,55,56]”
BackgroundOkazaki, I., Noro, T., Tsutsui, N., Yamanouchi, E., Kuroda, H., Nakano, M., Yokomori, H., & Inagaki, Y. (2014) · Cancers · doi:10.3390/cancers6031220 · Cited by 52 · see citing works
“This discrepancy may be based in the etiology of HCC, because the hypothesis of Figure 2 is based on HBV- or HCV-related HCC while Figure 3a is NASH-related HCC.”
BackgroundInfluentialHigh fat diet and exercise lead to a disrupted and pathogenic DNA methylome in mouse liver
Zhou, D., Hlady, R. A., Schafer, M. J., White, T. A., Liu, C., Choi, J.-H., Miller, J. D., Roberts, L. R., LeBrasseur, N. K., & Robertson, K. D. (2016) · Epigenetics · doi:10.1080/15592294.2016.1261239 · Cited by 52 · see citing works
- Authors
- Murphy, S. K., Yang, H., Moylan, C. A., Pang, H., Dellinger, A., Abdelmalek, M. F., Garrett, M. E., Ashley–Koch, A., Suzuki, A., Tillmann, H. L., Hauser, M. A., & Diehl, A. M.
- Affiliations
- Duke University (US)
- Corresponding author
- Diehl, Anna Mae
- ORCID
- Venue
- Gastroenterology
- Publisher
- Elsevier BV
- Published
- 2013-11
- Volume
- 145
- Issue
- 5
- Pages
- 1076-1087
- ISSN
- 0016-5085 (ISSN-L)
- PMC
- PMC3805742
- OpenAlex
- W2150020322
- Cited by
- 391
- References
- 48
- Citations by year
- 2026: 14 · 2025: 23 · 2024: 36 · 2023: 37 · 2022: 31 · 2021: 35 · 2020: 31 · 2019: 38 · 2018: 40 · 2017: 32 · 2016: 26 · 2015: 28 · 2014: 17 · 2013: 2 · 2012: 1
- FWCI
- 10.89
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Gastroenterology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- The HKU Scholars Hub (University of Hong Kong) (submittedVersion)
- Funders
- National Institutes of Health (5rc2aa019399-02)
- National Institute on Alcohol Abuse and Alcoholism (5RC2-AA019399, RC2-AA019399)
- National Institute of Diabetes and Digestive and Kidney Diseases (T32DK007568)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
- Health Sciences › Medicine › Epidemiology › Liver Disease Diagnosis and Treatment
- Health Sciences › Medicine › Hepatology › Liver physiology and pathology
- Keywords
- non-alcoholic fatty liver disease, DNA methylation, transcriptome, liver fibrosis, disease severity, differentially methylated CpG sites, gene expression, FGF2, MAT1A, caspase-1, one-carbon metabolism, NAFLD progression, non-invasive diagnosis
- MeSH terms
- Adult, Biopsy, Diagnosis, Differential, Fatty Liver, Female, Gene Expression Regulation, Humans, Liver, Male, Methionine Adenosyltransferase, Middle Aged, Severity of Illness Index, Cohort Studies, Disease Progression, CpG Islands, DNA Methylation, Caspase 1, Receptor, Fibroblast Growth Factor, Type 2, Transcriptome, Non-alcoholic Fatty Liver Disease
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