Hepatic Fat Accumulation Is Modulated by the Interaction between the rs738409 Variant in the PNPLA3 Gene and the Dietary Omega6/Omega3 PUFA Intake
Open accessAbstract
BACKGROUND: A single nucleotide polymorphism (SNP), the rs738409, in the patatin like phospholipase 3 gene (PNPLA3) has been recently associated with increased hepatic steatosis and ALT levels in adults and children. Given the potential role of PNPLA3 in fatty liver development, we aimed to explore whether the influence of PNPLA3 genotype on hepatic fat in obese youth might be modulated by dietary factors such as essential omega polyunsaturated fatty acids (PUFA) intake. MATERIALS AND METHODS: We studied 127 children and adolescents (56 boys, 71 girls; 58 Caucasians; 30 African Americans and 39 Hispanics; mean age 14.7±3.3; mean BMI 30.7±7.2). The dietary composition was assessed by the Nutrition Data System for Research (NDS-R version 2011). The patients underwent a MRI study to assess the liver fat content (HFF%), ALT measurement and the genotyping of the rs738409 SNP by automatic sequencing. RESULTS: As previously observed, HFF% and ALT levels varied according to the genotype in each ethnicity. ALT levels and HFF% were significantly influenced by the interaction between genotype and omega-6/omega-3 PUFA ratio (n-6/n-3), p = 0.003 and p = 0.002, respectively. HFF% and ALT levels were, in fact, related to the n-6/n-3 consumption only in subjects homozygote for the G allele of the rs738409 (r2 = 0.45, p = 0.001 and r2 = 0.40, p = 0.006, respectively). CONCLUSIONS: These findings suggest that the association of a high dietary n-6/n-3 PUFA with fatty liver and liver damage in obese youths may be driven by a predisposing genotype.
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- Authors
- Santoro, N., Savoye, M., Kim, G., Marotto, K., Shaw, M. M., Pierpont, B., & Caprio, S.
- Affiliations
- Yale University (US)
- Corresponding author
- Santoro, Nicola
- Caprio, Sonia
- Venue
- PLoS ONE
- Publisher
- Public Library of Science (PLoS)
- Published
- 2012-05-21
- Volume
- 7
- Issue
- 5
- Pages
- e37827
- ISSN
- 1932-6203 (ISSN-L)
- PMC
- PMC3357343
- OpenAlex
- W2002231036
- Cited by
- 108
- References
- 29
- Citations by year
- 2026: 1 · 2025: 4 · 2024: 8 · 2023: 11 · 2022: 9 · 2021: 6 · 2020: 10 · 2019: 1 · 2018: 8 · 2017: 7 · 2016: 7 · 2015: 17 · 2014: 10 · 2013: 8 · 2012: 1
- FWCI
- 8.62
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- PLoS ONE (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- American Heart Association (11CRP5620013)
- Yale University
- National Institutes of Health (28016, and K24, R01-HD)
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (R01-HD- 28016, R01HD028016, R01-HD40787, K24HD001464, R01HD040787, K24-HD01464)
- Yale Center for Clinical Investigation, Yale School of Medicine
- Topics
- Health Sciences › Medicine › Epidemiology › Liver Disease Diagnosis and Treatment
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Nutrition, Genetics, and Disease
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diet, Metabolism, and Disease
- Keywords
- PNPLA3, rs738409, hepatic steatosis, hepatic fat fraction, dietary polyunsaturated fatty acids, genetic susceptibility, gene-diet interaction, obesity, adolescents, children, alanine aminotransferase, ethnic differences
- MeSH terms
- Acyltransferases, Adipose Tissue, Adolescent, Child, Dietary Fats, Fatty Liver, Female, Genotype, Humans, Lipase, Liver, Male, Membrane Proteins, Obesity, Fatty Acids, Omega-3, Polymorphism, Single Nucleotide, Fatty Acids, Omega-6, Phospholipases A2, Calcium-Independent, Gene-Environment Interaction
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