New genetic forms of obesity, type 2 diabetes discovered

Chuck Bednar for – @BednarChuck

By sequencing the DNA of an extremely obese young woman and members of her family, a team of researchers from Imperial College London has discovered a new inherited form of obesity and type 2 diabetes.

The scientists, who have published their findings in the journal PLOS One, explained there are a large number of genes involved in the regulation of body weight, and more than 30 known genes that can cause changes in a person’s DNA sequence, leading to weight gain.

They added that there are also many genes that can cause type 2 diabetes when altered, and that these conditions can be inherited through families in much the same way that ailments like cystic fibrosis or Huntington’s disease. It’s unclear exactly what percentage of severe obesity and type 2 diabetes is linked to genetic causes, but the UCL team has found a new trigger.

“There are now an increasing number of single-gene causes of obesity and diabetes known,” said lead author Professor Alex Blakemore of the UCL Department of Medicine. “We don’t know how many more have yet to be discovered, or what proportion of the severely obese people in our population have these diseases – it is not possible to tell just by looking.”

Lack of appetite controlling protein

In addition to having an increased appetite, which led to severe weight issues starting during her childhood, the young woman involved in the study had type 2 diabetes, learning difficulties, and reproductive problems. The authors found that she had inherited two copies of a harmful genetic mutation, prohibiting her from producing the protein carboxypeptidase-E (CPE).

CPE, the researchers explained, is an enzyme involved in the processing of numerous hormones and brain transmitters helping to control appetite, insulin levels, and reproductive system functions. Previous studies have shown that CPE deficiency in mice can cause obesity, diabetes, and memory issues, but this marks the first time the condition has ever been found in a human.

Since this is a recessive condition, the altered sequence would have to have been inherited from both parents. In this case, the woman’s parents are cousins, which gave her a relatively high likelihood of inheriting the same genetic change from both parents. Furthermore, she had an older brother who had similar symptoms and had died at the age of 21.

“Finding a genetic cause for the patient’s problems has helped her and her family to understand and manage her condition better,” said author Dr. Sanne Alsters, also from the UCL Department of Medicine. “We can also look at members of her family with one abnormal copy of the gene to see they are affected in more subtle ways that could increase their risk of obesity.”

Professor Blakemore added that genetic tests should be made available for patients with severe obesity. “If people are diagnosed with a genetic condition like this one,” she said, “we can look for other possible symptoms, and offer genetic advice to other family members if they want this. Diagnosis is very valuable to the patient. It helps to set realistic expectations, and can help them get the best possible treatment.”


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