TY - JOUR
T1 - Impact of a diet and activity health promotion intervention on regional patterns of DNA methylation
AU - Hibler, Elizabeth
AU - Huang, Lei
AU - Andrade, Jorge
AU - Spring, Bonnie
N1 - Funding Information:
This study was registered as NCT01249989 at clinicaltrials.gov on November 20, 2010 (https://clinicaltrials.gov/ct2/show/NCT01249989). This work was supported by NHLBI R01 HL075451 (Spring), P30CA60553 (Robert H. Lurie Comprehensive Center, Northwestern University) NCATS UL1TR000150 (Northwestern University), NIH 5UL1TR002389-02 (University of Chicago), and NIH P30CA014599 (The University of Chicago Comprehensive Cancer Center).
Publisher Copyright:
© 2019 The Author(s).
PY - 2019/9/11
Y1 - 2019/9/11
N2 - Background: Studies demonstrate the impact of diet and physical activity on epigenetic biomarkers, specifically DNA methylation. However, no intervention studies have examined the combined impact of dietary and activity changes on the blood epigenome. The objective of this study was to examine the impact of the Make Better Choices 2 (MBC2) healthy diet and activity intervention on patterns of epigenome-wide DNA methylation. The MBC2 study was a 9-month randomized controlled trial among adults aged 18-65 with non-optimal levels of health behaviors. The study compared three 12-week interventions to (1) simultaneously increase exercise and fruit/vegetable intake, while decreasing sedentary leisure screen time; (2) sequentially increase fruit/vegetable intake and decrease leisure screen time first, then increase exercise; (3) increase sleep and decrease stress (control). We collected blood samples at baseline, 3 and 9 months, and measured DNA methylation using the Illumina EPIC (850 k) BeadChip. We examined region-based differential methylation patterns using linear regression models with the false discovery rate of 0.05. We also conducted pathway analysis using gene ontology (GO), KEGG, and IPA canonical pathway databases. Results: We found no differences between the MBC2 population (n = 340) and the subsample with DNA methylation measured (n = 68) on baseline characteristics or the impact of the intervention on behavior change. We identified no differentially methylated regions at baseline between the control versus intervention groups. At 3 versus 9 months, we identified 154 and 298 differentially methylated regions, respectively, between controls compared to pooled samples from sequential and simultaneous groups. In the GO database, we identified two gene ontology terms related to hemophilic cell adhesion and cell-cell adhesion. In IPA analysis, we found pathways related to carcinogenesis including PI3K/AKT, Wnt/β-catenin, sonic hedgehog, and p53 signaling. We observed an overlap between 3 and 9 months, including the GDP-l-fucose biosynthesis I, methylmalonyl metabolism, and estrogen-mediated cell cycle regulation pathways. Conclusions: The results demonstrate that the MBC2 diet and physical activity intervention impacts patterns of DNA methylation in gene regions related to cell cycle regulation and carcinogenesis. Future studies will examine DNA methylation as a biomarker to identify populations that may particularly benefit from incorporating health behavior change into plans for precision prevention.
AB - Background: Studies demonstrate the impact of diet and physical activity on epigenetic biomarkers, specifically DNA methylation. However, no intervention studies have examined the combined impact of dietary and activity changes on the blood epigenome. The objective of this study was to examine the impact of the Make Better Choices 2 (MBC2) healthy diet and activity intervention on patterns of epigenome-wide DNA methylation. The MBC2 study was a 9-month randomized controlled trial among adults aged 18-65 with non-optimal levels of health behaviors. The study compared three 12-week interventions to (1) simultaneously increase exercise and fruit/vegetable intake, while decreasing sedentary leisure screen time; (2) sequentially increase fruit/vegetable intake and decrease leisure screen time first, then increase exercise; (3) increase sleep and decrease stress (control). We collected blood samples at baseline, 3 and 9 months, and measured DNA methylation using the Illumina EPIC (850 k) BeadChip. We examined region-based differential methylation patterns using linear regression models with the false discovery rate of 0.05. We also conducted pathway analysis using gene ontology (GO), KEGG, and IPA canonical pathway databases. Results: We found no differences between the MBC2 population (n = 340) and the subsample with DNA methylation measured (n = 68) on baseline characteristics or the impact of the intervention on behavior change. We identified no differentially methylated regions at baseline between the control versus intervention groups. At 3 versus 9 months, we identified 154 and 298 differentially methylated regions, respectively, between controls compared to pooled samples from sequential and simultaneous groups. In the GO database, we identified two gene ontology terms related to hemophilic cell adhesion and cell-cell adhesion. In IPA analysis, we found pathways related to carcinogenesis including PI3K/AKT, Wnt/β-catenin, sonic hedgehog, and p53 signaling. We observed an overlap between 3 and 9 months, including the GDP-l-fucose biosynthesis I, methylmalonyl metabolism, and estrogen-mediated cell cycle regulation pathways. Conclusions: The results demonstrate that the MBC2 diet and physical activity intervention impacts patterns of DNA methylation in gene regions related to cell cycle regulation and carcinogenesis. Future studies will examine DNA methylation as a biomarker to identify populations that may particularly benefit from incorporating health behavior change into plans for precision prevention.
KW - DNA methylation
KW - Diet
KW - Lifestyle
KW - Physical activity
KW - Randomized trial
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U2 - 10.1186/s13148-019-0707-0
DO - 10.1186/s13148-019-0707-0
M3 - Article
C2 - 31506096
AN - SCOPUS:85072052702
VL - 11
JO - Clinical Epigenetics
JF - Clinical Epigenetics
SN - 1868-7075
IS - 1
M1 - 133
ER -