Growing evidence has implicated DNA methylation (DNAm) in the regulation of body adiposity; a recent epigenome-wide association study (EWAS) identified a genetic variant determining DNAm at the SREBF1 gene that affected body mass index (BMI).
In the present study, we tested interactions between DNAm variant rs752579 and methylation metabolism-related B-vitamins (folate, vitamin B2, vitamin B6, and vitamin B12) on longitudinal change in BMI in the Women’s Health Initiative Memory Study (WHIMS).
A total of 5687 white women aged 65–79 from WHIMS with genotyping data on SNP rs752579 were included in the analysis. B-vitamins intakes were estimated by a self-report semi-quantitative food frequency questionnaire. BMI was measured at baseline and 6-year follow-up.
We found significant interactions between the SREBF1 rs752579 genotype and intake of food source B-vitamins on 6-year change in BMI (p interaction <0.01 for all). BMI changes (kg/m2) per DNAm-increasing (C) allele were −0.29, 0.06, and 0.11 within subgroups of increasing tertiles of food source folate intake; and the corresponding BMI changes (kg/m2) were −0.25, −0.01, and 0.15 for vitamin B2 intake; −0.17, −0.16, and 0.21 for vitamin B6 intake; and −0.12, −0.23, and 0.26 for vitamin B12 intake, respectively. Similar gene–diet interaction patterns were observed on the change in body weight.
Our data suggest that habitual intake of food source B-vitamins may modify the effect of DNAm-related variant on long-term adiposity change.
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We appreciate all the participants in WHIMS for their continued cooperation.
The study was supported by grants from the National Heart, Lung, and Blood Institute (HL071981, HL034594, HL126024), the National Institute of Diabetes and Digestive and Kidney Diseases (DK115679, DK091718, DK100383, DK078616), the Boston Obesity Nutrition Research Center (DK46200), and United States—Israel Binational Science Foundation Grant 2011036. LQ was a recipient of the American Heart Association Scientist Development Award (0730094N).
XL and LQ conceived and designed the study. LQ acquired the data. XL performed data analyses and drafted the manuscript. DS, MZ, and TH provided statistical assistance. All authors contributed to the interpretation of the results and critical revision of the manuscript for important intellectual content and approved the final version of the manuscript. LQ is the guarantor and takes responsibility for the integrity of the data and the accuracy of the data analyses.
Conflict of interest
The authors declare that they have no conflict of interest.