In kids’ DNA, study hunts link between their health and what their mothers ate years ago

EMPHASIS, short for Epigenetic Mechanism linking Pre-Conceptional Nutrition and Health Assessed in India and Sub-Saharan Africa, is an Indo-UK-Gambia collaboration, the first study in humans that hopes to understand the epigenetic mechanisms underpinning the long-term impact of maternal nutrition on offspring health.

Investigators are following two groups — one of 1,200 children in India and the other of 200 in the Gambia. The study protocol was published in the October 2017 issue of the journal BMC Nutrition. At present, DNA samples from Mumbai and the Gambia are being analysed at the Centre for Cellular and Molecular Biology (CCMB).

The study owes its beginning to research some 20 years ago when the head of the diabetes unit of Pune’s KEM Hospital, Prof Chittaranjan Yajnik, and others showed that Indian diabetic patients were younger, shorter and thinner but centrally obese (higher waist-hip ratio). This gave rise to a “thin-fat insulin resistant Indian” concept, leading to further research.

A study of the foetal origins of adult disease found that children who were born small but grew big were most affected. This finding was followed up with a study on what factors influenced the growth of Indian babies. The Pune Maternal Nutrition Study found that low maternal vitamin B12 but high folate status leaves the baby predisposed to risk factors for type-2 diabetes – insulin resistance and adiposity.

While mothers and their babies (now adolescents) are still being tracked as part of the B12 intervention programme, a trial was also conducted during 2006-12 among more than 6,000 women living in Mumbai slums. Under the Mumbai Maternal Nutrition Project, they were given, before pregnancy, a daily micronutrient snack (green leafy vegetables, fruit and milk). Over 2,000 women, who became pregnant, were given iron and folic acid supplements; the babies born showed a 48-g increase in birth weight. The maternal nutritional intervention also reduced the prevalence of gestational diabetes. Now, the children of these mothers are being studied at age five-seven (2013-2018) for skeletal development, cardio-metabolic risk markers and cognitive function.

All this research has now led to the EMPHASIS study. “We are now profiling genome-wide DNA methylation in children whose mothers participated in trials in Mumbai and rural Gambia before and during pregnancy,” Prof Giriraj Chandak, group leader at CCMB Hyderabad, told The Indian Express. Prof Yajnik said: “Our findings have opened a new door in this branch and it could have important implications in controlling diabetes and heart disease in the country.”

What has made scientists hopeful is the result of another trial, published in the November 2017 issue of the journal Epigenomics. Here, researchers including Dr Dilip Yadav, Prof Yajnik and others investigated the molecular changes associated with B12 supplementation, alone and with folic acid, among adolescents in Pune, and observed changes in DNA methylation for one year. They observed that only vitamin B12 supplementation influences, through methylation, the regulation of several important genes associated with Type-2 diabetes.

The usual assumption is that the DNA sequence in an individual determines the function of a particular gene – which is true, the scientists note. “However, despite having a similar sequence, different individuals may have different functions of a gene. This may be possible due to some modifications – such as DNA methylation,” Prof Chandak said. “This is a modification of DNA that regulates the function of a gene. Genes are the structural units of DNA that determine a specific function, so it is important to understand what regulates a gene function.”

Prof Yajnik cited the instance of a mouse’s agousti gene. “All mammals have a gene called agousti. When this gene is completely unmethylated, its coat is yellow and it is obese and prone to diabetes. When the gene is methylated – the coat colour is brown and the mouse has a low disease risk,” Prof Yajnik said.