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Obesity prevention gene found in Pakistan and Greenland

Wednesday January 10th, 2018

A newly analysed gene is linked to the risk of obesity via the malfunction of a protein controlling appetite control, researchers reported last night.

A research team from Imperial College London, UK, who had previously found genetic links to obesity in about 30% of cases among children in Pakistan, looked further at the link between genes and obesity.

They investigated inherited recessive mutations using genome sequencing, and found mutations in a specific gene related to obesity, called adenylate cyclase 3 (ADCY3).

Simultaneously researchers in Denmark reported discovering the same gene in Greenland – finding a link to obesity when it was inactivated. They could not find the same problem elsewhere in Europe.

The mutations can lead to abnormal appetite control, diabetes, and problems with the sense of smell, the researchers say.

In Nature Genetics on Monday (8 January), the team write: "Here we identify and functionally characterise homozygous mutations in the ADCY3 gene encoding adenylate cyclase 3 in children with severe obesity from consanguineous Pakistani families.

"These findings highlight ADCY3 as an important mediator of energy homeostasis and an attractive pharmacological target in the treatment of obesity."

Lead researcher, Professor Philippe Froguel, said: "Early studies into ADCY3 tested mice that were bred to lack that gene, found that these animals were obese and also lacked the ability to smell, known as anosmia. When we tested our patients, we found that they also had anosmia, again showing a link to mutations in ADCY3.

"Obesity is not always gluttony, as is often suggested, and I think we should have a positive outlook considering the new treatments that are becoming possible."

Associate Professor Niels Grarup, of the University of Copenhagen, Denmark, also reported in the journal: “We have found a gene, ADCY3, which predisposes Greenlanders to obesity and diabetes when it is inactive. This appears to be unique to the Greenlandic population.”

Fellow researcher Professor Torben Hansen said: “We are pretty convinced that it is this Greenlandic gene that impacts on obesity and the risk of developing diabetes. Because in seven individuals the gene is not expressed at all, and this really causes problems.”

Saeed, S. et al. Loss-of-function mutations in ADCY3 cause monogenic severe obesity. Nature Genetics 8 January 2018; doi: 10.1038/s41588-017-0023-6 [abstract]

Loss-of-function variants in ADCY3 increase risk of obesity and type 2 diabetes Nature Genetics 8 January 2018; doi:10.1038/s41588-017-0022-7 [abstract]

Tags: Asia | Diet & Food | Europe | Genetics

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