Table 2.
Summary of human studies investigating the interaction between diet with DNA methylation levels at circadian clock genes.
| Authors (Ref) |
Sample Size | Study Design | Methylation Profiles in Target Genes | Evidence |
|---|---|---|---|---|
| Milagro et al., 2012 [101] |
N = 20 Normal weight (BMI < 25 kg/m2), N = 20 overweight/obese (BMI = 29–35 kg/m2) N = 20 morbidly obese women (BMI > 40 kg/m2), aged 25 to 53 years |
Cross-sectional study (28 weeks of treatment) |
CLOCK
BMAL1 PER2 |
Association between methylation status of CpG sites located in CLOCK, BMAL1, and PER2 with obesity, MetS. The methylation status of different CpG sites in CLOCK and PER2 has been proposed as biomarkers of weight loss success. |
| Ramos-Lopez et al., 2018 [104] |
N = 474 adults belonging to the MENA project | Cross-sectional study |
RORA
PRKAG2 PER3 BHLHE40 FBXL3 RORA CREB1 PRKAG2 PRKAG2 |
Correlation between DNA methylation patterns at six circadian rhythm pathway genes with BMI. Correlation between methylation signatures at cg09578018 (RORA), cg24061580 (PRKAG2), cg01180628 (BHLHE40), and cg10059324 (PER3) with insulin resistance (p < 0.0001) and mean arterial blood pressure (p < 0.0001). Relevant correlations between methylation at cg09578018 (RORA) and cg01180628 (BHLHE40) with total energy and carbohydrate intakes (p < 0.05). |
| Samblas et al., 2016 [102] |
N = 61 women (BMI = 28.6 ± 3.4 kg/m2; age: 42.2 ± 11.4 years) | Cross-sectional study Weight loss treatment (nutritional program based on a Mediterranean dietary pattern) |
BMAL1 CLOCK NR1D1 |
The energy-restricted intervention modified the methylation levels of different CpG sites in BMAL1 and NR1D1. The changes in BMAL1 methylation level with the intervention, positively correlated with the eveningness profile (p = 0.019). The baseline methylation at BMAL1 positively correlated with energy (p = 0.047) and carbohydrate (p = 0.017) intake and negatively correlated with the effect of the weight loss intervention on TC (p = 0.032) and low-density lipoprotein cholesterol (p = 0.005). Significant and positive correlations were found between changes in methylation levels in the CpG region of BMAL1 due to the intervention and changes in serum lipids (p < 0.05). |
MENA: Methyl Epigenome Network Association (MENA) project; BMI: body mass index; TC: total cholesterol.