Abstract

Variability in plasma carotenoids may be attributable to several factors including genetic variants and lipid profile. Until now, the impact of DNA methylation on this variability has not been widely studied. Weighted gene correlation network analysis (WGCNA) is a systems biology method used for finding gene clusters (modules) with highly correlated methylation levels and for relating them to phenotypic traits. The objective of the present study was to examine the role of DNA methylation in the relationship between plasma total carotenoid concentrations and lipid profile using WGCNA in 48 healthy subjects. Genome-wide DNA methylation levels of 20,687 out of 472,245 CpG sites in blood leukocytes were associated with total carotenoid concentrations. Using WGCNA, nine co-methylation modules were identified. A total of 2734 hub genes (17 unique top hub genes) were potentially related to lipid profile. This study provides evidence for the potential implications of gene co-methylation in the relationship between plasma carotenoids and lipid profile. Further studies and validation of the hub genes are needed.

Highlights

  • Cardiometabolic (CM) diseases comprise conditions ranging from insulin resistance and metabolic syndrome to cardiovascular disease and type-2 diabetes [1]

  • This study provides evidence for the potential implications of gene co-methylation in the relationship between plasma carotenoids and lipid profile

  • Lower circulating carotenoid concentrations are associated with lower plasma total cholesterol (TC), LDL-cholesterol (LDL-C), and HDL-cholesterol (HDL-C)

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Summary

Introduction

Cardiometabolic (CM) diseases comprise conditions ranging from insulin resistance and metabolic syndrome to cardiovascular disease and type-2 diabetes [1]. Healthy eating, including the consumption of fruits and vegetables, is associated with a favorable CM health [2]. Carotenoids, which are reliable biomarkers of fruit and vegetable intakes, are composed of hundreds of fat-soluble pigments [3]. Six main carotenoids (α-carotene, β-carotene, β-cryptoxanthin, lutein, lycopene, and zeaxanthin) represent over 95% of total circulating carotenoids in human [4,5]. Variability among individuals in circulating carotenoids may be due to several factors, including age, sex, body weight, genetics, and lipid profile [3]. Lower circulating carotenoid concentrations are associated with lower plasma total cholesterol (TC), LDL-cholesterol (LDL-C), and HDL-cholesterol (HDL-C)

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