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

Abstract

Background: Many epigenetic loci have been associated with plasma triglyceride (TG) levels, but epigenetic connections between those loci and dietary exposures are largely unknown. This study aimed to characterize the epigenetic links between diet, lifestyle, and TG.Methods: We first conducted an epigenome-wide association study (EWAS) for TG in the Framingham Heart Study Offspring population (FHS, n = 2,264). We then examined relationships between dietary and lifestyle-related variables, collected four times in 13 years, and differential DNA methylation sites (DMSs) associated with the last TG measures. Third, we conducted a mediation analysis to evaluate the causal relationships between diet-related variables and TG. Finally, we replicated three steps to validate identified DMSs associated with alcohol and carbohydrate intake in the Genetics of Lipid-Lowering Drugs and Diet Network (GOLDN) study (n = 993).Results: In the FHS, the EWAS revealed 28 TG-associated DMSs at 19 gene regions. We identified 102 unique associations between these DMSs and one or more dietary and lifestyle-related variables. Alcohol and carbohydrate intake showed the most significant and consistent associations with 11 TG-associated DMSs. Mediation analyses demonstrated that alcohol and carbohydrate intake independently affect TG via DMSs as mediators. Higher alcohol intake was associated with lower methylation at seven DMSs and higher TG. In contrast, increased carbohydrate intake was associated with higher DNA methylation at two DMSs (CPT1A and SLC7A11) and lower TG. Validation in the GOLDN further supports the findings.Conclusion: Our findings imply that TG-associated DMSs reflect dietary intakes, particularly alcoholic drinks, which could affect the current cardiometabolic risk via epigenetic changes. This study illustrates a new method to map epigenetic signatures of environmental factors for disease risk. Identification of epigenetic markers of dietary intake can provide insight into an individual’s risk of cardiovascular disease and support the application of precision nutrition.Clinical Trial Registration:www.ClinicalTrials.gov, the Framingham Heart Study (FHS), NCT00005121; the Genetics of Lipid Lowering Drugs and Diet Network (GOLDN), NCT01023750.

Epigenetics of Early Cardiometabolic Disease: Mechanisms and Precision Medicine

“…Therefore, it holds great promise in discovering novel markers for precision nutrition and potential targets for precision interventions. 76–81…”

“…Therefore, it holds great promise in discovering novel markers for precision nutrition and potential targets for precision interventions. [76][77][78][79][80][81] Cardiovascular health (CVH) from young adulthood is strongly associated with an individual's future risk of CVD and total mortality. Therefore, defining epigenomic biomarkers of lifelong CVH exposure and understanding their roles in CVD development may help develop preventive and therapeutic strategies for CVD.…”

Elevated blood remnant cholesterol and triglycerides are causally related to the risks of cardiometabolic multimorbidity

“…However, the importance of triglyceride-rich lipoproteins, namely remnant cholesterol and triglycerides, for progression from first cardiometabolic disease to multimorbidity is not fully understood. It is noteworthy that diet, like fat and cholesterol intake, and lifestyle factors might substantially influence triglyceride-rich lipoprotein metabolism [19][20][21] . The complex interplay between lipid species might also confound the observational relationships between triglyceriderich lipoproteins and cardiometabolic diseases 22 .…”