SIX decades after their pregnant mothers were starved during the second world war, the genes of Dutch men and women retain chemical changes that may put them at risk of diabetes and cancer.
Our genes are subject to 鈥渆pigenetic鈥� changes that affect the way we produce proteins. For example, environmental influences can cause changes in the number of chemical 鈥渃aps鈥� called methyl groups that are added to DNA bases. These help determine how much protein the gene makes.
The caps can last a lifetime, and may even be passed to offspring. In 2006, researchers at University College London and Ume氓 University in Sweden found a link between the nutrition and smoking habits of a group of men and the health of their sons and grandsons, which they attributed to epigenetics (New Scientist, 6 January 2006, p 10). Other studies have found that if pregnant mice skimp on foods important for DNA methylation, their pups鈥� genes carry fewer methyl caps.
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To look for chemical evidence of epigenetics in people, in New York, and colleagues studied 60 people who were conceived while German forces occupying the Netherlands were preventing food reaching local people. 鈥淵ou can鈥檛 do a lab experiment in people but you can maybe learn from a war situation that in many ways resembles a lab experiment,鈥� Lumey says.
鈥淵ou can鈥檛 do a lab experiment in people but you can maybe learn from a war situation that resembles a lab experiment鈥�
The food shortage meant pregnant women ate as little as 500 calories a day between December 1944 and May 1945. The team looked at children born to these women, focusing on the IGF2 gene, which is involved in growth. To minimise differences in genetics and upbringing, they compared it with the same gene in a brother or sister conceived during more plentiful times.
The IGF2 genes of the famine babies carried about 5 per cent fewer methyl caps than their siblings, on average (Proceedings of the National Academy of Sciences, ). A lack of caps could crank up IGF2 expression enough to make a biological difference, says Lumey鈥檚 colleague Bastiaan Heijmans of in the Netherlands.
A preliminary analysis found no link between IGF2 methylation and body weight, but a reduction in the number of methyl caps has been linked to colorectal cancer in humans. Heijmans speculates that fewer caps may encourage a fetus to extract more energy from food; this might help during starvation but lead to diabetes when calories are no longer scarce.
Though interested to see how diet affects IGF2, geneticist at Baylor College of Medicine in Houston, Texas, doubts that the change is large enough to have a significant effect on the production of IGF2 protein. Other genes may be more affected, he suggests.
