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Anorexia linked to genetic mutation

16 September 2013
Appeared in BioNews 722

The eating disorder anorexia nervosa has been linked, somewhat unexpectedly, to variants of a gene involved in cholesterol regulation.

A study of over 3,000 people shows that versions of the gene EPHX2 are strongly associated with the condition. The findings suggest that the likelihood of developing anorexia may be tied to both genetic and social factors.

Professor Nicholas Schork of The Scripp Research Institute in California, USA, a senior investigator for the study, said: 'These findings point in a direction that probably no one would have considered taking before'.

Around one in 250 women and one in 2,000 men will develop anorexia nervosa during their lives, a 2004 report from the National Institute for Health and Care Excellence suggests. Patients restrict their eating severely, often continuing to believe they are overweight despite being dangerously malnourished. The resulting severe emaciation can be fatal and some consider anorexia as one of the most lethal psychiatric diseases.

Anorexia was long considered to be caused by psychological or social factors such as stress, pressures at the onset of puberty and cultural pressures. But twin studies have suggested that genetic factors may be an important influence.

In this study researchers initially probed the genomes of 334 anorexia patients. After drawing up a list of more than 150 candidate genes already linked to feeding behaviour or metabolism, they found a few that showed statistical signs of a linkage with anorexia.

One of the strongest associations was with variations of EPHX2, which codes for an enzyme that regulates cholesterol metabolism. The link was confirmed after several replication studies.

'We thought that with further studies this EPHX2 finding might go away, or appear less compelling, but we just kept finding evidence to suggest that it plays a role in anorexia', said Professor Schork.

The data was also compared with data from long term heart disease research showing that mutations in EPHX2 can cause changes in the relationship between cholesterol levels and weight gain.

It is not yet known how disruption of cholesterol metabolism might contribute to development of anorexia. Some studies have found that patients with anorexia nervosa have elevated cholesterol levels, while other research suggests that elevated cholesterol levels are linked with heightened mood for some people.

Discussing potential mechanisms, Professor Schork said: 'The hypothesis would be that in some anorexics the normal metabolism of cholesterol is disrupted, which could influence their mood as well as their ability to survive despite severe caloric restriction'.

SOURCES & REFERENCES
Anorexia could have genetic link, study claims
Daily Telegraph |  12 September 2013
Does anorexia have a genetic link? New theory suggests the disorder may not be purely down to social pressures
Daily Mail |  12 September 2013
Evidence for the role of EPHX2 gene variants in anorexia nervosa
Molecular Psychiatry |  3 September 2013
New Genetic Clue to Anorexia
Science Daily (press release) |  11 September 2013
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