Serum microRNAs explain discordance of non-alcoholic fatty liver disease in monozygotic and dizygotic twins: a prospective study
Open accessAbstract
Objective: In the setting where two individuals are genetically similar, epigenetic mechanisms could account for discordance in the presence or absence of non-alcoholic fatty liver disease (NAFLD). This study investigated if serum microRNAs (miRs) could explain discordance in NAFLD. Design: This is a cross-sectional analysis of a prospective cohort study of 40 (n=80) twin-pairs residing in Southern California. All participants underwent a standardised research visit, liver MRI using proton-density fat fraction to quantify fat content and miR profiling of their serum. Results: Among the 40 twin-pairs, there were 6 concordant for NAFLD, 28 were concordant for non-NAFLD and 6 were discordant for NAFLD. The prevalence of NAFLD was 22.5% (18/80). Within the six discordant twins, a panel of 10 miRs differentiated the twin with NAFLD from the one without. Two of these miRs, miR-331-3p and miR-30c, were also among the 21 miRs that were different between NAFLD and non-NAFLD groups (for miR-331-3p: 7.644±0.091 vs 8.057±0.071, respectively, p=0.004; for miR-30c: 10.013±0.126 vs 10.418±0.086, respectively, p=0.008). Both miRs were highly heritable (35.9% and 10.7%, respectively) and highly correlated with each other (R=0.90, p=2.2×10−16) suggesting involvement in a common mechanistic pathway. An interactome analysis of these two miRs showed seven common target genes. Conclusions: Using a novel human twin-study design, we demonstrate that discordancy in liver fat content between the twins can be explained by miRs, and that they are heritable.
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miR-331-3p and miR-30c can distinguish between twins where one develops MASLD and the other does not.
“For instance, miR-331-3p and miR-30c can distinguish between twins, with one developing MASLD and the other not (168).”
From Found in translation—Fibrosis in metabolic dysfunction–associated steatohepatitis (MASH) (2023) · cites this paper as [168]
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Biomarkers of NAFLD progression: a lipidomics approach to an epidemic
Gorden, D. L., Myers, D. S., Ivanova, P. T., Fahy, E., Maurya, M. R., Gupta, S., Min, J., Spann, N. J., McDonald, J. G., Kelly, S. L., et al. (2015) · Journal of Lipid Research · doi:10.1194/jlr.p056002 · Cited by 372 · see citing works
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Global burden of NAFLD and NASH: trends, predictions, risk factors and prevention
Younossi, Z., Anstee, Q. M., Marietti, M., Hardy, T., Henry, L., Eslam, M., George, J., & Bugianesi, E. (2018) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/nrgastro.2017.109 · Cited by 5,249 · see citing works
Mechanisms and disease consequences of nonalcoholic fatty liver disease
Loomba, R., Friedman, S. L., & Shulman, G. I. (2021) · Cell · doi:10.1016/j.cell.2021.04.015 · Cited by 2,002 · see citing works
Self-citationLoomba, R., Seguritan, V., Li, W., Long, T., Klitgord, N., Bhatt, A., Dulai, P. S., Caussy, C., Bettencourt, R., Highlander, S. K., et al. (2017) · Cell Metabolism · doi:10.1016/j.cmet.2017.04.001 · Cited by 1,123 · see citing works
Self-citationA Gut Microbiome Signature for Cirrhosis Due to Nonalcoholic Fatty Liver Disease
Caussy, C., Tripathi, A., Humphrey, G., Bassirian, S., Singh, S., Faulkner, C., Bettencourt, R., Rizo, E., Richards, L., Xu, Z. Z., et al. (2019) · Nature Communications · doi:10.1038/s41467-019-09455-9 · Cited by 338 · see citing works
Self-citationCaussy, C., Hsu, C., Lo, M., Liu, A., Bettencourt, R., Ajmera, V. H., Bassirian, S., Hooker, J., Sy, E., Richards, L., et al. (2018) · Hepatology · doi:10.1002/hep.29892 · Cited by 205 · see citing works
Self-citationFound 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
Lonardo, A., Mantovani, A., Lugari, S., & Targher, G. (2020) · Annals of Hepatology · doi:10.1016/j.aohep.2020.03.001 · Cited by 150 · see citing works
Soto-Angona, Ó., Anmella, G., Valdés-Florido, M. J., De Uribe-Viloria, N., Carvalho, A. F., Penninx, B. W. J. H., & Berk, M. (2020) · BMC Medicine · doi:10.1186/s12916-020-01713-8 · Cited by 122 · see citing works
- Authors
- Zarrinpar, A., Gupta, S., Maurya, M. R., Subramaniam, S., & Loomba, R.
- Affiliations
- University of California San Diego (US)
- San Diego Supercomputer Center (US)
- Corresponding author
- Loomba, Rohit
- Venue
- Gut
- Publisher
- BMJ
- Published
- 2015-05-22
- Volume
- 65
- Issue
- 9
- Pages
- 1546-1554
- ISSN
- 0017-5749 (ISSN-L)
- 1468-3288
- PMC
- PMC5089367
- OpenAlex
- W1943556640
- Cited by
- 88
- References
- 1
- Citations by year
- 2026: 1 · 2025: 6 · 2024: 3 · 2023: 5 · 2022: 8 · 2021: 7 · 2020: 12 · 2019: 8 · 2018: 11 · 2017: 9 · 2016: 9 · 2015: 8
- FWCI
- 9.68
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Gut (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- HighWire Press Open Archive (submittedVersion)
- Funders
- National Institutes of Health (KL2TR000099)
- National Heart, Lung, and Blood Institute (R01HL106579, R01HL108735)
- National Institute of Diabetes and Digestive and Kidney Diseases (K08DK102902, T32DK007202, K23DK090303)
- National Center for Advancing Translational Sciences
- Topics
- Health Sciences › Medicine › Epidemiology › Liver Disease Diagnosis and Treatment
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › MicroRNA in disease regulation
- Health Sciences › Medicine › Pathology and Forensic Medicine › Alcohol Consumption and Health Effects
- Keywords
- non-alcoholic fatty liver disease, monozygotic twins, dizygotic twins, serum microRNA, miR-331-3p, miR-30c, heritability, epigenetics, liver fat, proton density fat fraction, protein-protein interaction network, biomarkers
- MeSH terms
- California, Cross-Sectional Studies, Female, Humans, Liver, Magnetic Resonance Imaging, Male, Middle Aged, Prospective Studies, Twins, Dizygotic, Twins, Monozygotic, Prevalence, Gene Expression Profiling, MicroRNAs, Epigenesis, Genetic, Non-alcoholic Fatty Liver Disease
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