Mother's diet affects the 'silencing' of her child's genes

(Press-News.org) A mother's diet before conception can permanently affect how her child's genes function, according to a study published in Nature Communications.

The first such evidence of the effect in humans opens up the possibility that a mother's diet before pregnancy could permanently affect many aspects of her children's lifelong health.

Researchers from the MRC International Nutrition Group, based at the London School of Hygiene & Tropical Medicine and MRC Unit, The Gambia, utilised a unique 'experiment of nature' in rural Gambia, where the population's dependence on own grown foods and a markedly seasonal climate impose a large difference in people's dietary patterns between rainy and dry seasons.

Through a selection process involving over 2,000 women, the researchers enrolled pregnant women who conceived at the peak of the rainy season (84 women) and the peak of the dry season (83 women). By measuring the concentrations of nutrients in their blood, and later analysing blood and hair follicle samples from their 2-8 month old infants, they found that a mother's diet before conception had a significant effect on the properties of her child's DNA.

While a child's genes are inherited directly from their parents, how these genes are expressed is controlled through 'epigenetic' modifications to the DNA. One such modification involves tagging gene regions with chemical compounds called methyl groups and results in silencing the genes. The addition of these compounds requires key nutrients including folate, vitamins B2, B6 and B12, choline and methionine.

Experiments in animals have already shown that environmental influences before conception can lead to epigenetic changes that affect the offspring. A 2003 study found that a female mouse's diet can change her offspring's coat colour by permanently modifying DNA methylation.1 But until this latest research, funded by the Wellcome Trust and the MRC, it was unknown whether such effects also occur in humans.

Senior author Dr Branwen Hennig, Senior Investigator Scientist at the MRC Gambia Unit and the London School of Hygiene & Tropical Medicine, said: "Our results represent the first demonstration in humans that a mother's nutritional well-being at the time of conception can change how her child's genes will be interpreted, with a life-long impact."

The researchers found that infants from rainy season conceptions had consistently higher rates of methyl groups present in all six genes they studied, and that these were linked to various nutrient levels in the mother's blood. Strong associations were found with two compounds in particular (homocysteine and cysteine), and the mothers' body mass index (BMI) had an additional influence. However, although these epigenetic effects were observed, their functional consequences remain unknown.

Professor Andrew Prentice, Professor of International Nutrition at the London School of Hygiene & Tropical Medicine, and head of the Nutrition Theme at the MRC Unit, The Gambia, said: "Our on-going research is yielding strong indications that the methylation machinery can be disrupted by nutrient deficiencies and that this can lead to disease. Our ultimate goal is to define an optimal diet for mothers-to-be that would prevent defects in the methylation process. Pre-conceptional folic acid is already used to prevent defects in embryos. Now our research is pointing towards the need for a cocktail of nutrients, which could come from the diet or from supplements."

Dr Rob Waterland of Baylor College of Medicine in Houston, who conducted the epigenetic analyses said: "We selected these gene regions because our earlier studies in mice had shown that establishment of DNA methylation at metastable epialleles is particularly sensitive to maternal nutrition in early pregnancy."

The authors note that their study was limited by including only one blood sampling point during early pregnancy, but estimates of pre-conception nutrient concentrations were calculated using results from non-pregnant women sampled throughout a whole calendar year. The authors also plan to increase the sample size in further studies.

INFORMATION: This study was funded by the Wellcome Trust, UK; the Medical Research Council (MRC); the UK Department for International Development (DFID); the NIH/National Institute of Diabetes and Digestive and Kidney Diseases, USA; and the USDA, USA. Additional institutions involved in the study included the University of North Carolina, USA; University of British Columbia, Canada; and SRI International, USA.

To request a copy of the paper or to interview the authors, please contact Joel Winston in the London School of Hygiene & Tropical Medicine press office on press@lshtm.ac.uk or +44(0)207 927 2802.

To interview Dr Rob Waterland, please contact Dipali Pathak at the Baylor College of Medicine office of public affairs on pathak@bcm.edu or +1 713-798-4712

Paper reference: Maternal nutrition at conception modulates DNA methylation of human metastable epialleles. Paula Dominguez-Salas, Sophie E. Moore, Maria S. Baker, Andrew W. Bergen, Sharon E. Cox, Roger A. Dyer, Anthony J. Fulford, Yongtao Guan, Eleonora Laritsky, Matt Silver, Gary E. Swan, Steven H. Zeisel, Sheila M. Innis, Robert A. Waterland, Andrew M. Prentice & Branwen J. Hennig. Nature Communications. DOI: 10.1038/ncomms4746

If you wish to provide a link to this paper for your readers, please use the following, which will go live at the time the embargo lifts: http://dx.doi.org/10.1038/ncomms4746

1 Study by Robert A. Waterland and Randy L. Jirtle, Duke University Medical Center. Published in Molecular and Cellular Biology, August 2003

About the London School of Hygiene & Tropical Medicine

The London School of Hygiene & Tropical Medicine is a world-leading centre for research and postgraduate education in public and global health, with 3,900 students and more than 1,000 staff working in over 100 countries. The School is one of the highest-rated research institutions in the UK, and was recently cited as the world's leading research-focused graduate school. Our mission is to improve health and health equity in the UK and worldwide; working in partnership to achieve excellence in public and global health research, education and translation of knowledge into policy and practice. http://www.lshtm.ac.uk

About the MRC International Nutrition Group

On 1 April 2014, the MRC International Nutrition Group (MRC ING see http://www.ing.mrc.ac.uk) became fully integrated into the MRC Unit, The Gambia. Nutrition will become a fourth theme within The Gambia Unit and will be led by Professor Andrew Prentice. The MRC's unit in The Gambia has an international reputation for ground-breaking research into some of the leading causes of morbidity and mortality in the tropics, and its research has led to some of the most outstanding successes in tropical medicine. http://www.mrc.gm/

About the Wellcome Trust

The Wellcome Trust is a global charitable foundation dedicated to achieving extraordinary improvements in human and animal health. It supports the brightest minds in biomedical research and the medical humanities. The Trust's breadth of support includes public engagement, education and the application of research to improve health. It is independent of both political and commercial interests. http://www.wellcome.ac.uk

About the Baylor College of Medicine

Baylor College of Medicine in Houston is recognized as a premier academic health sciences center and is known for excellence in education, research and patient care. It is the only private medical school in the greater southwest and is ranked 21st among medical schools for research and 12th for primary care by U.S. News & World Report. Baylor is listed 19th among all U.S. medical schools for National Institutes of Health funding and number one in Texas. Located in the Texas Medical Center, Baylor has affiliations with seven teaching hospitals and jointly owns and operates CHI St. Luke's Baylor St. Luke's Medical Center. Currently, Baylor trains more than 3,000 medical, graduate, nurse anesthesia, physician assistant and orthotics students, as well as residents and post-doctoral fellows. http://www.bcm.edu

About the Medical Research Council

The Medical Research Council has been at the forefront of scientific discovery to improve human health. Founded in 1913 to tackle tuberculosis, the MRC now invests taxpayers' money in some of the best medical research in the world across every area of health. Twenty-nine MRC-funded researchers have won Nobel prizes in a wide range of disciplines, and MRC scientists have been behind such diverse discoveries as vitamins, the structure of DNA and the link between smoking and cancer, as well as achievements such as pioneering the use of randomised controlled trials, the invention of MRI scanning, and the development of a group of antibodies used in the making of some of the most successful drugs ever developed. Today, MRC-funded scientists tackle some of the greatest health problems facing humanity in the 21st century, from the rising tide of chronic diseases associated with ageing to the threats posed by rapidly mutating micro-organisms. http://www.mrc.ac.uk