Researchers said on Tuesday they had found a gene linked to type 1 diabetes, which starts in childhood and leaves people dependent on insulin for life.
They said their finding sheds light on the incurable disease, which affects more than 800,000 people in the United States alone, and might offer better ways to treat it than simply injecting insulin.
The gene is not the sole cause of type 1 diabetes, also known as insulin-dependent diabetes mellitus (IDDM), but targeting the defect may help prevent its onset, the researchers said.
"Prior to our finding, there had been consensus amongst geneticists for only 2 other genes in type 1 diabetes, and these were first found over 20 years ago. So its a lot of hard work and a long process but we are now making definite progress and it should be a lot quicker from here," Grant Morahan of the Walter and Eliza Hall Institute for Medical Research in Melbourne, Australia, who led the study, said in an interview.
Type 1 diabetes is an autoimmune disease, caused when the body's defenses mistakenly attack the pancreas. Patients lose the cells that produce insulin, which is vital to making use of sugar and fat in the food.
Without precise doses of insulin, they die, or can lose vision and limbs and develop other health problems.
Morahan and colleagues knew of work in mice specially bred to develop diabetes that turned up one of the genes involved in the production of interleukin-12 (IL-12), an immune-system signaling chemical or cytokine.
When injected into the mice, IL-12 activates immune T-cells known to attack the pancreas in diabetes. In diabetes-prone mice, they found a very slight change in a gene affecting IL-12 called IDDM18.
"When people administered IL-12 to diabetes-prone NOD mice, the incidence of diabetes increased but if they gave agents which reduced IL-12 then fewer mice became diabetic," Morahan said in the interview, conducted by e-mail.
FAMILIES SHOWED SIMILAR CHANGES
Morahan and colleagues then looked at families with type 1 diabetes to see if they had a similar change. "We tested a total of 249 affected sibpairs (brothers and sister pairs) ... and an additional 120 families obtained from the British Diabetes Association," they wrote in their report, published in the journal Nature Genetics.
They found many had a similar change. They also found, when they grew cells with that mutation, that they produced more IL-12 than normal.
This higher-than-normal production of IL-12 could be kick-starting the destruction of the vital pancreatic cells.
Morahan said it seems clear the genetic change is not the sole cause of diabetes. "This disease is very complicated genetically and we are beginning to see that different genes contribute to susceptibility in different people with type 1 diabetes," he said.
"The susceptibility variant we describe is actually quite common in the population," he added.
"That suggests it is not a 'disease gene' per se but is actually doing a good job for most of us, and that it is only when this variant is found in a certain combination with other type 1 diabetes susceptibility genes and environmental factors that it leads to diabetes. This is different from other less common genetic diseases that have rare "disease genes".
Luciano Adorini, of Roche Milano Richerche, an Italian research lab associated with Swiss drug giant Roche, said this may lead to screening and treatment for type 1 diabetes and might eventually lead to treatments for other autoimmune diseases, which include rheumatoid arthritis.