The chronic disease—which affects about 2 million people in the U.S. and is diagnosed in 13,000 children each year—is an autoimmune disorder, in which disease-fighting cells attack pancreatic cells that produce insulin, a hormone that regulates the level of glucose (sugar) in the blood. A deficit of insulin causes blood glucose levels to spike, which can lead to, among other things, kidney failure, retina damage, heart disease and, in some cases, death. The ability to assess a child's risk of developing the disease or to speed its diagnosis is crucial to managing the illness.
"[Type 1 diabetes] is clearly is one of these complex genetic disorders," involving mutations in several genes acting in concert to predispose someone to the condition, says Hakon Hakonarson, director of The Children's Hospital of Philadelphia's Center for Applied Genomics and lead author of the new study, published this week in the online edition of Nature. "The notion is that people believe that about approximately half of it is explained by genetics and half of it is environmental."
Hakonarson's team conducted a genome-wide scan of about 1,000 pediatric diabetes patients, 1,200 healthy children and 1,000 parents of diabetics to track down any links between the illness and 550,000 known mutations found in their genetic code. They turned up many previously implicated genes—at least eight had been fingered prior to this study—as well as three previously undiscovered changes in one gene on chromosome 16 (of each cell's 23 pairs) that appeared to be related to the condition. "There were three markers in this KIAA0350 gene," Hakonarson says, "all sitting in the middle of the gene."
The researchers successfully replicated their findings in a separate, independent sample of 1,600 diabetes patients in whom they also discovered these three so-called flavors or flaws. According to Hakonarson, two of the gene variations—acting alone—appear to increase one's odds of developing diabetes by 50 percent. Ironically, the third mutation discovered appeared to shield against the disease, decreasing the risk by as much as 50 percent.
Hakonarson says that the function of the protein produced by KIAA0350 is unknown, but that there will likely "be a race among multiple labs [(his included)] to find [that] out." He speculates that it is involved with the mechanism that activates cells that trigger the immune system to destroy insulin-producing cells.
"This was what you call a sort of fast-track phase," Hakonarson says about the new study, in which he and his team identified and characterized only the strongest signals in the genome-wide analysis. Next up: researchers are set examine the 2,000 strongest signals to see if they can identify a "gene network" that may be behind type 1 diabetes.