Diabetes :: Complex genetic risk factors behind type 2 diabetes

A UK collaboration of scientists has identified three new genes that predispose individuals to develop type 2 diabetes 1, bringing scientists a step closer towards understanding what causes this complex disease.

The study – jointly led by researchers at the University of Oxford and the Peninsula Medical School, Exeter, and forming part of the Wellcome Trust Case Control Consortium 2 – looked at over 2 billion pieces of genetic data, 6000 people with type 2 diabetes and 8000 controls to track down these three genes. In addition, they confirmed the link between the disease and a further two previously identified genes.

The findings, published online today in the journal Science 3, bring the total number of genes known to be involved in type 2 diabetes to nine, including the FTO gene reported by the same UK group two weeks ago. The FTO gene influences individual risk of type 2 diabetes through its effect on weight and obesity.

Type 2 diabetes occurs as a result of a failure of the body to produce enough insulin to maintain normal levels of glucose (sugar) in the blood. This failure is usually compounded by a reduction in the capacity of the insulin released to work properly in tissues such as muscle and fat (known as insulin resistance). It is a major cause of heart disease and stroke, as well as blindness and kidney failure.

There are currently around 200 million people worldwide who have type 2 diabetes, yet its underlying cause is poorly understood, limiting both treatment and prevention. Lifestyle factors such as poor diet and lack of exercise have been known for some time to increase the risk of developing the disease, but scientists are becoming increasingly aware of the role played by genetics.

For each of the three genes described in the paper, the researchers have found that there are two common ‘versions’, one of which is associated with an increased risk of developing type 2 diabetes and the other with reduced risk. Each high-risk version increases the risk of type 2 diabetes by between 10 and 20 per cent. All are common in the general population.

“This research helps us to understand that, for most people at least, an individual’s risk of developing diabetes as they get older is influenced by a number of genes, as well as by their environment,” says Professor Mark McCarthy from the University of Oxford, one of the lead authors of the paper. “Clearly, the more ‘high risk’ alleles a person inherits, the higher the likelihood that they will go on to develop diabetes.”

The exact role of the genes that have been implicated by these studies is still uncertain. However, two of them appear to be involved in the development, function and regeneration of insulin-producing beta cells found within the pancreas. This finding is likely to help to answer a long-standing controversy in the diabetes field concerning the extent to which a reduced number of pancreatic beta-cells (as opposed to reduced function) contributes to the development of diabetes.

“We now have significantly more pieces to the jigsaw that will help us understand the mechanisms behind type 2 diabetes,” says Professor Andrew Hattersley of the Peninsula Medical School, also a lead author on the paper. “Each piece of new knowledge takes us a step closer towards a future with improved prevention and treatment of this very significant condition.”

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