| Title: | Genetic risk accentuates dietary effects on hepatic steatosis, inflammation and fibrosis in a population-based cohort |
| Journal: | Journal of Hepatology |
| Published: | 4 Apr 2024 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/38582304/ |
| DOI: | https://doi.org/10.1016/j.jhep.2024.03.045 |
| URL: | http://www.journal-of-hepatology.eu/article/S0168827824002307/pdf |
Publication 9969
WARNING: the interactive features of this website use CSS3, which your browser does not support. To use the full features of this website, please update your browser.
Abstract
BACKGROUND & AIMS: Steatotic liver disease (SLD), characterized by elevated liver fat content (LFC), is influenced by genetics and diet. However, whether diet has differential effect based on genetic risk is not well-characterized. We aimed to determine how genetic factors interact with diet to affect SLD in a large national biobank.</p>
METHODS: We included UK Biobank participants with dietary intake measured by 24-hour recall and genotyping. The primary predictors were dietary pattern, PNPLA3-rs738409-G, TM6SF2-rs58542926-T, a 16-variant hepatic steatosis polygenic risk score (PRS), and gene-environment interactions. The primary outcome was LFC, and secondary outcomes were iron-controlled T1 time (cT1, a measure of liver inflammation and fibrosis) and liver-related events/mortality.</p>
RESULTS: 21,619 participants met inclusion criteria. In non-interaction models, Mediterranean diet and intake of fruit/vegetables/legumes and fish associated with lower LFC, while higher red/processed meat intake and all genetic predictors associated with higher LFC. In interaction models, all genetic predictors interacted with Mediterranean diet and fruit/vegetable/legume intake; the steatosis PRS interacted with fish intake; and TM6SF2 genotype interacted with red/processed meat intake, to affect LFC. Dietary effects on LFC were up to 3.8 times as high in PNPLA3-rs738409-GG vs. -CC individuals, and 1.4-3.0 times as high in the top vs. bottom quartile of the steatosis PRS. Gene-diet interactions were stronger in participants with vs. without overweight. The steatosis PRS interacted with Mediterranean diet and fruit/vegetable/legume intake to affect cT1 and most dietary and genetic predictors associated with risk of liver-related events or mortality by age 70.</p>
CONCLUSIONS: Effects of diet on LFC and cT1 were markedly accentuated in patients at increased genetic risk for SLD, implying dietary interventions may be more impactful in these populations.</p>
8 Authors
- Vincent L Chen
- Xiaomeng Du
- Antonino Oliveri
- Yanhua Chen
- Annapurna Kuppa
- Brian D Halligan
- Michael A Province
- Elizabeth K Speliotes
Enabling scientific discoveries that improve human health