Chemical modifications to genes over a person's lifetime may influence body mass without changing their inherited DNA sequence, a new study has found. This is the first time epigenetic changes - long-standing chemical alterations to genes - have been linked to body weight and obesity.
The research, published in the journal Science Translational Medicine, adds to increasing evidence that genes alone do not determine body characteristics. The environment may also affect these traits by altering gene behaviour.
Professor Andrew Feinberg and his team from John Hopkins University School of Medicine, US, mapped DNA methylation, an epigenetic change known to switch off neighbouring genes, over 11 years in 74 adults with varying body shapes. These people were examined for regions where epigenetic patterns differed between group members by an unusually large extent.
The group were screened again in 2002 to determine which methylation sequences had remained constant. Professor Feinberg's team reasoned any variations would have occurred early in life and become fixed, therefore having a long-term influence on traits, including body weight. 119 of the 227 methylated areas were the same in 1991 and 2002. Professor Feinberg's team matched these to people's body shape and it became apparent 13 methylated genes were more prominent in overweight volunteers.
'We don't know yet the degree to which genes and environment add up to give us these stable methylation changes, but we believe both are important', said Professor Feinberg.
One of the 13 genes, PRKG1, is known to play a role when insects and nematode worms search for food. The methylated genes also include those responsible for metalloproteinase enzyme production, already linked to obesity in mice. By identifying methylated genes linked to obesity, scientists could provide new ways to test a person's likelihood of becoming overweight later in life.
'The results do suggest the importance of including epigenetic analysis with genetic analysis in personalised medicine research to predict risk', explained Professor Feinberg.
The team admit they do not know whether the epigenetic marks increase the risk of obesity or are a side effect of it, but future studies may illustrate how genes and the environment interact to determine disease risk.
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