The impact of alcoholic drinks and dietary factors on epigenetic markers associated with triglyceride levels

Authors: Lai, Chao Qiang; Parnell, Laurence; Lee, Yu Chi; ZENG, HAIHAN - Jean Mayer Human Nutrition Research Center On Aging At Tufts University; SMITH, CAREN - Jean Mayer Human Nutrition Research Center On Aging At Tufts University; MCKEOWAN, NICOLA - Jean Mayer Human Nutrition Research Center On Aging At Tufts University; ORDOVAS, JOSE - Jean Mayer Human Nutrition Research Center On Aging At Tufts University

Submitted to: Frontiers in Genetics
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 1/30/2023
Publication Date: 2/15/2023
Citation: Lai, C., Parnell, L.D., Lee, Y., Zeng, H., Smith, C., Mckeowan, N.M., Ordovas, J.M. 2023. The impact of alcoholic drinks and dietary factors on epigenetic markers associated with triglyceride levels. Frontiers in Genetics. https://doi.org/10.3389/fgene.2023.1117778.
DOI: https://doi.org/10.3389/fgene.2023.1117778

Interpretive Summary: Diet and lifestyle habits can modify specific elements of DNA in a process known as epigenetics and, more specifically, DNA methylation. These modifications alter gene activity, and, potentially, human health. However, we know little about the relationship between diet and lifestyle habits and epigenetic status concerning metabolic health. In this study, we examined DNA methylation sites (DMS) associated with plasma triglyceride levels (TG), a proxy for metabolic health, and dietary and lifestyle measures over 13 years in the Framingham Heart Study. We found that several dietary measures were significantly correlated with 19 TG-related DMS. Among them, alcohol and carbohydrate intake showed the strongest associations. Using a particular statistical method called mediation analysis, our analyses suggest that alcohol modified the epigenetic status of seven genes inducing increases in plasma TG concentrations. In contrast, carbohydrate intake modified the methylation status of two genes resulting in plasma TG lowering. This study shows that dietary factors can leave specific signatures on the genome. The characterization of such signatures will be crucial to identify mechanisms by which diet affects an individual’s health. Future studies are needed to explore the proper balance between alcohol and carbohydrate intake at the individual level to maintain healthy blood TG levels.

Technical Abstract: Background: Current evidence has shown that environmental and lifestyle factors are associated with DNA methylation patterns. However, mechanisms underlying the relationship between diet and other exposures and epigenetic profiles are less understood. To understand the unique connections between dietary intake and lifestyle factors on disease risk, we conducted epigenetic mapping of diet and lifestyle habits for plasma triglyceride concentrations (TG) by investigating links between lifestyle, including diet, and methylation marks with TG. Methods: We first conducted an epigenome-wide association study (EWAS) for TG in the Framingham Heart Study Offspring population (n=2,178). We then examined the relationships between dietary and lifestyle-related variables, collected over 13 years, and differential DNA methylation sites (DMS) associated with the last TG measures (exam 8). Second, we conducted a mediation analysis to evaluate potential causal relationships between diet-related variables and TG. Results: The EWAS revealed 28 TG-associated DMS at 19 regions (e.g., ABCG1, CPT1A, DHCR24, GARS, NCORS, PFKFB3, PHGDH, PPP2R2B, RNF145, SARS, SLC1A5, SLC43A1, SLC7A11 SREBF1, TXNIP, ZFHX3). We identified 427 significant associations between these DMSs and one or more dietary and lifestyle-related variables after accounting for multiple testing. The most significant and consistent associations between 11 TG-associated DMSs and diet were alcohol (g/day) and carbohydrate intake (% total energy), with P-values ranging from 10-4 to 10-70. Mediation analyses demonstrated that alcohol and carbohydrate intake independently affect TG via DMSs as mediators. For seven of the 19 identified DMS regions, higher alcohol intake was associated with lower methylation and higher TG. In contrast, increased carbohydrate intake was associated with higher DNA methylation at two epigenetic loci (CPT1A and SLC7A11) and lower TG. Conclusions: Our findings imply that TG-associated DMSs reflect dietary intakes that could affect cardiometabolic disease risk via epigenetic changes, specifically through their impact on DNA methylation.