News Reader.info

ABSTRACT BACKGROUND 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). OBJECTIVE 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). DESIGN 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. RESULT 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. CONCLUSIONS Our data suggest that habitual intake of food source

B-vitamins may modify the effect of DNAm-related variant on long-term adiposity change. Access through your institution Buy or subscribe This is a preview of subscription content, access via

your institution ACCESS OPTIONS Access through your institution Subscribe to this journal Receive 12 print issues and online access $259.00 per year only $21.58 per issue Learn more Buy

this article * Purchase on SpringerLink * Instant access to full article PDF Buy now Prices may be subject to local taxes which are calculated during checkout ADDITIONAL ACCESS OPTIONS: *

Log in * Learn about institutional subscriptions * Read our FAQs * Contact customer support SIMILAR CONTENT BEING VIEWED BY OTHERS COMMON VARIANTS IN THE _CD36_ GENE ARE ASSOCIATED WITH

DIETARY FAT INTAKE, HIGH-FAT FOOD CONSUMPTION AND SERUM TRIGLYCERIDES IN A COHORT OF QUEBEC ADULTS Article 11 February 2021 MENDELIAN RANDOMIZATION ON THE ASSOCIATION OF OBESITY WITH VITAMIN

D: GUANGZHOU BIOBANK COHORT STUDY Article 08 November 2022 INTERACTION OF GENETIC AND ENVIRONMENTAL FACTORS FOR BODY FAT MASS CONTROL: OBSERVATIONAL STUDY FOR LIFESTYLE MODIFICATION AND

GENOTYPING Article Open access 23 June 2021 REFERENCES * Ogden CL, Carroll MD, Kit BK, Flegal KM. Prevalence of childhood and adult obesity in the United States, 2011-2012. JAMA.

2014;311:806–14. Article  CAS  PubMed  PubMed Central  Google Scholar  * van Dijk SJ, Molloy PL, Varinli H, Morrison JL, Muhlhausler BS. Epigenetics and human obesity. Int J Obes (Lond).

2015;39:85–97. Article  Google Scholar  * Lindgren CM, Heid IM, Randall JC, Lamina C, Steinthorsdottir V, Qi L, et al. Genome-wide association scan meta-analysis identifies three loci

influencing adiposity and fat distribution. PLoS Genet. 2009;5:e1000508. Article  PubMed  PubMed Central  Google Scholar  * Thorleifsson G, Walters GB, Gudbjartsson DF, Steinthorsdottir V,

Sulem P, Helgadottir A, et al. Genome-wide association yields new sequence variants at seven loci that associate with measures of obesity. Nat Genet. 2009;41:18–24. Article  CAS  PubMed 

Google Scholar  * Qi L, Kraft P, Hunter DJ, Hu FB. The common obesity variant near MC4R gene is associated with higher intakes of total energy and dietary fat, weight change and diabetes

risk in women. Hum Mol Genet. 2008;17:3502–8. Article  CAS  PubMed  PubMed Central  Google Scholar  * Speliotes EK, Willer CJ, Berndt SI, Monda KL, Thorleifsson G, Jackson AU, et al.

Association analyses of 249,796 individuals reveal eighteen new loci associated with body mass index. Nat Genet. 2010;42:937–48. Article  CAS  PubMed  PubMed Central  Google Scholar  * Qi L,

Cho YA. Gene-environment interaction and obesity. Nutr Rev. 2008;66:684–94. Article  PubMed  Google Scholar  * Qi Q, Chu AY, Kang JH, Jensen MK, Curhan GC, Pasquale LR, et al.

Sugar-sweetened beverages and genetic risk of obesity. N Engl J Med. 2012;367:1387–96. Article  CAS  PubMed  PubMed Central  Google Scholar  * Zhang X, Qi Q, Zhang C, Smith SR, Hu FB, Sacks

FM, et al. FTO genotype and 2-year change in body composition and fat distribution in response to weight-loss diets: the POUNDS LOST Trial. Diabetes. 2012;61:3005–11. Article  CAS  PubMed 

PubMed Central  Google Scholar  * Jones PA. The role of DNA methylation in mammalian epigenetics. Science. 2001;293:1068–70. Article  CAS  PubMed  Google Scholar  * Dick KJ, Nelson CP,

Tsaprouni L, Sandling JK, Aïssi D, Wahl S, et al. DNA methylation and body-mass index: a genome-wide analysis. Lancet. 2014;383:1990–8. Article  CAS  PubMed  Google Scholar  * Martínez JA,

Milagro FI, Claycombe KJ, Schalinske KL. Epigenetics in adipose tissue, obesity, weight loss, and diabetes 1, 2. Adv Nutr. 2014;5:71–81. Article  PubMed  PubMed Central  Google Scholar  *

Aronica L, Joan A, Brennan K, Mi J, Gardner C, Haile RW, et al. Systematic review of studies of DNA methylation in the context of a weight loss intervention. Epigenomics. 2017;9:769–87.

Article  CAS  PubMed  Google Scholar  * Robertson KD. DNA methylation and human disease. Nat Rev Genet. 2005;6:597–10. Article  CAS  PubMed  Google Scholar  * Mendelson MM, Marioni RE,

Joehanes R, Liu C, Hedman ÅK, Aslibekyan S, et al. Association of body mass index with DNA methylation and gene expression in blood cells and relations to cardiometabolic disease: a

Mendelian randomization approach. PLoS Med. 2017;14:1–30. Article  Google Scholar  * Ly A, Hoyt L, Crowell J, Kim Y-I. Folate and DNA methylation. Antioxid Redox Signal. 2012;17:302–26.

Article  CAS  PubMed  Google Scholar  * Anderson OS, Sant KE, Dolinoy DC. Nutrition and epigenetics: an interplay of dietary methyl donors, one-carbon metabolism and DNA methylation. J Nutr

Biochem. 2012;23:853–9. Article  CAS  PubMed  PubMed Central  Google Scholar  * Shelnutt KP, Kauwell GPA, Gregory JF III, Maneval DR, Quinlivan EP, Theriaque DW, et al.

Methylenetetrahydrofolate reductase 677C--T polymorphism affects DNA methylation in response to controlled folate intake in young women. J Nutr Biochem. 2004;15:554–60. Article  CAS  PubMed

  Google Scholar  * Huang T, Zheng Y, Qi Q, Xu M, Ley SH, Li Y et al. DNA methylation variants at HIF3A locus, B-vitamin intake, and long-term weight change: gene-diet interactions in two

U.S. Cohorts. Diabetes 2015. https://doi.org/10.2337/db15-0264. Article  CAS  PubMed  PubMed Central  Google Scholar  * Design of the Women’s Health Initiative Clinical Trial and

Observational Study. Control Clin Trials. 1998;19:61–109. * Anderson GL, Manson J, Wallace R, Lund B, Hall D, Davis S, et al. Implementation of the Women’s Health Initiative study design.

Ann Epidemiol. 2003;13:S5–17. Article  PubMed  Google Scholar  * Shumaker SA, Reboussin BA, Espeland MA, Rapp SR, McBee WL, Dailey M, et al. The Women’s Health Initiative Memory Study

(WHIMS): a trial of the effect of estrogen therapy in preventing and slowing the progression of dementia. Control Clin Trials. 1998;19:604–21. Article  CAS  PubMed  Google Scholar  *

Patterson RE, Kristal AR, Tinker LF, Carter RA, Bolton MP, Agurs-Collins T. Measurement characteristics of the Women’s Health Initiative food frequency questionnaire. Ann Epidemiol.

1999;9:178–87. Article  CAS  PubMed  Google Scholar  * Kessler DA, Shalala DE. Federal Register/Vol. 61, No. 44/Tuesday, March 5, 1996/Rules and Regulations. 1996; 61. * Agnew-Blais JC,

Wassertheil-Smoller S, Kang JH, Hogan PE, Coker LH, Snetselaar LG, et al. Folate, vitamin B-6, and vitamin B-12 intake and mild cognitive impairment and probable dementia in the Women’s

Health Initiative Memory Study. J Acad Nutr Diet. 2015;115:231–41. Article  PubMed  Google Scholar  * Meyer A-M, Evenson KR, Morimoto L, Siscovick D, White E. Test-retest reliability of the

Women’s Health Initiative physical activity questionnaire. Med Sci Sports Exerc. 2009;41:530–8. Article  PubMed  PubMed Central  Google Scholar  * Qi L. Gene-diet interaction and weight

loss. Curr Opin Lipidol. 2014;25:27–34. Article  CAS  PubMed  PubMed Central  Google Scholar  * Main AM, Gillberg L, Jacobsen AL, Nilsson E, Gjesing AP, Hansen T, et al. DNA methylation and

gene expression of HIF3A: cross-tissue validation and associations with BMI and insulin resistance. Clin Epigenetics. 2016;8:89. Article  PubMed  PubMed Central  Google Scholar  * Strable

MS, Ntambi JM. Genetic control of de novo lipogenesis: role in diet-induced obesity. Crit Rev Biochem Mol Biol. 2010;45:199–14. Article  CAS  PubMed  PubMed Central  Google Scholar  * Qi L.

Mendelian randomization in nutritional epidemiology. Nutr Rev. 2009;67:439–50. Article  PubMed  Google Scholar  * Bates CJ, Mansoor MA, Gregory J, Pentiev K, Prentice A. Correlates of plasma

homocysteine, cysteine and cysteinyl-glycine in respondents in the British National Diet and Nutrition Survey of young people aged 4-18 years, and a comparison with the survey of people

aged 65 years and over. Br J Nutr. 2002;87:71–79. Article  CAS  PubMed  Google Scholar  * De Laet C, Wautrecht JC, Brasseur D, Dramaix M, Boeynaems JM, Decuyper J, et al. Plasma homocysteine

concentration in a Belgian school-age population. Am J Clin Nutr. 1999;69:968–72. Article  PubMed  Google Scholar  * Gunanti IR, Marks GC, Al-Mamun A, Long KZ. Low serum vitamin B-12 and

folate concentrations and low thiamin and riboflavin intakes are inversely associated with greater adiposity in Mexican American children. J Nutr. 2014;144:2027–33. Article  CAS  PubMed 

Google Scholar  * Hassapidou M, Fotiadou E, Maglara E, Papadopoulou SK. Energy intake, diet composition, energy expenditure, and body fatness of adolescents in northern Greece. Obesity

(Silver Spring). 2006;14:855–62. Article  Google Scholar  * Selhub J. Folate, vitamin B12 and vitamin B6 and one carbon metabolism. J Nutr Health Aging. 2002;6:39–42. CAS  PubMed  Google

Scholar  * Vasicek TJ, Zeng L, Guan XJ, Zhang T, Costantini F, Tilghman SM. Two dominant mutations in the mouse fused gene are the result of transposon insertions. Genetics. 1997;147:777–86.

CAS  PubMed  PubMed Central  Google Scholar  * Waterland RA, Dolinoy DC, Lin J-R, Smith CA, Shi X, Tahiliani KG. Maternal methyl supplements increase offspring DNA methylation at Axin

Fused. Genesis. 2006;44:401–6. Article  CAS  PubMed  Google Scholar  * Duhl DM, Vrieling H, Miller KA, Wolff GL, Barsh GS. Neomorphic agouti mutations in obese yellow mice. Nat Genet.

1994;8:59–65. Article  CAS  PubMed  Google Scholar  * Waterland RA, Jirtle RL. Transposable elements: targets for early nutritional effects on epigenetic gene regulation. Mol Cell Biol.

2003;23:5293–300. Article  CAS  PubMed  PubMed Central  Google Scholar  * Pufulete M, Al-Ghnaniem R, Khushal A, Appleby P, Harris N, Gout S, et al. Effect of folic acid supplementation on

genomic DNA methylation in patients with colorectal adenoma. Gut . 2005;54:648–53. Article  CAS  PubMed  PubMed Central  Google Scholar  * Cravo ML, Pinto AG, Chaves P, Cruz JA, Lage P,

Nobre Leitao C, et al. Effect of folate supplementation on DNA methylation of rectal mucosa in patients with colonic adenomas: correlation with nutrient intake. Clin Nutr. 1998;17:45–49.

Article  CAS  PubMed  Google Scholar  * Cravo M, Fidalgo P, Pereira AD, Gouveia-Oliveira A, Chaves P, Selhub J, et al. DNA methylation as an intermediate biomarker in colorectal cancer:

modulation by folic acid supplementation. Eur J Cancer Prev. 1994;3:473–9. Article  CAS  PubMed  Google Scholar  * Kim YI, Baik HW, Fawaz K, Knox T, Lee YM, Norton R, et al. Effects of

folate supplementation on two provisional molecular markers of colon cancer: a prospective, randomized trial. Am J Gastroenterol. 2001;96:184–95. Article  CAS  PubMed  Google Scholar  *

Cooney CA, Dave AA, Wolff GL. Maternal methyl supplements in mice affect epigenetic variation and DNA methylation of offspring. J Nutr. 2002;132:2393S–400S. Article  CAS  PubMed  Google

Scholar  * Vineis P, Chuang S-C, Vaissiere T, Cuenin C, Ricceri F, Johansson M, et al. DNA methylation changes associated with cancer risk factors and blood levels of vitamin metabolites in

a prospective study. Epigenetics. 2011;6:195–201. Article  CAS  PubMed  Google Scholar  * Hoyo C, Murtha AP, Schildkraut JM, Jirtle RL, Demark-Wahnefried W, Forman MR, et al. Methylation

variation at IGF2 differentially methylated regions and maternal folic acid use before and during pregnancy. Epigenetics. 2011;6:928–36. Article  CAS  PubMed  PubMed Central  Google Scholar

  * Willett WC, Sampson L, Stampfer MJ, Rosner B, Bain C, Witschi J, et al. Reproducibility and validity of a semiquantitative food frequency questionnaire. Am J Epidemiol. 1985;122:51–65.

Article  CAS  PubMed  Google Scholar  * Perneger TV. What’s wrong with Bonferroni adjustments. BMJ. 1998;316:1236–8. Article  CAS  PubMed  PubMed Central  Google Scholar  Download references

ACKNOWLEDGEMENTS We appreciate all the participants in WHIMS for their continued cooperation. FUNDING 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). AUTHOR

CONTRIBUTIONS 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. AUTHOR INFORMATION AUTHORS AND AFFILIATIONS * Department of Epidemiology, School

of Public Health and Tropical Medicine, Tulane University, New Orleans, LA, USA Xiang Li, Tiange Wang, Min Zhao, Tao Huang, Dianjianyi Sun, Liyuan Han, Hoirun Nisa, Yoriko Heianza & Lu

Qi * Epidemiology Domain, Saw Swee Hock School of Public Health, National University of Singapore, Singapore, Singapore Tao Huang * Department of Public Health, Faculty of Medicine and

Health Sciences, State Islamic University, Jakarta, Indonesia Hoirun Nisa * Children’s Hospital New Orleans, New Orleans, LA, USA Xiaoyun Shang * Department of Nutrition, Harvard T.H. Chan

School of Public Health, Boston, MA, USA Lu Qi * Department of Medicine, Channing Division of Network Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, USA Lu Qi

Authors * Xiang Li View author publications You can also search for this author inPubMed Google Scholar * Tiange Wang View author publications You can also search for this author inPubMed 

Google Scholar * Min Zhao View author publications You can also search for this author inPubMed Google Scholar * Tao Huang View author publications You can also search for this author

inPubMed Google Scholar * Dianjianyi Sun View author publications You can also search for this author inPubMed Google Scholar * Liyuan Han View author publications You can also search for

this author inPubMed Google Scholar * Hoirun Nisa View author publications You can also search for this author inPubMed Google Scholar * Xiaoyun Shang View author publications You can also

search for this author inPubMed Google Scholar * Yoriko Heianza View author publications You can also search for this author inPubMed Google Scholar * Lu Qi View author publications You can

also search for this author inPubMed Google Scholar CORRESPONDING AUTHOR Correspondence to Lu Qi. ETHICS DECLARATIONS CONFLICT OF INTEREST The authors declare that they have no conflict of

interest. ELECTRONIC SUPPLEMENTARY MATERIAL SUPPLEMENTAL TABLE 1 RIGHTS AND PERMISSIONS Reprints and permissions ABOUT THIS ARTICLE CITE THIS ARTICLE Li, X., Wang, T., Zhao, M. _et al._ DNA

methylation variant, B-vitamins intake and longitudinal change in body mass index. _Int J Obes_ 43, 468–474 (2019). https://doi.org/10.1038/s41366-018-0106-1 Download citation * Received: 16

November 2017 * Revised: 03 April 2018 * Accepted: 09 April 2018 * Published: 17 May 2018 * Issue Date: March 2019 * DOI: https://doi.org/10.1038/s41366-018-0106-1 SHARE THIS ARTICLE Anyone

you share the following link with will be able to read this content: Get shareable link Sorry, a shareable link is not currently available for this article. Copy to clipboard Provided by

the Springer Nature SharedIt content-sharing initiative