Pediatrics researchers at The Children’s Hospital of Philadelphia and McGill University identified a gene variant that raises a child’s risk for type 1 diabetes. The research adds a new gene to the four previously discovered for type 1 diabetes.
The investigators compared the genomes of 563 patients with type 1 diabetes with those of 1,146 matched control subjects. The results were combined with those obtained from an independent analysis of 483 family trios, in which the genomes of a child with the disease and both parents were examined.
The researchers confirmed the four previously identified locations for genes contributing to the disease but also uncovered a new type 1 diabetes locus on chromosome 16, occupied by a gene called KIAA0350. The team then replicated this discovery in yet another independent cohort of 1,333 children from the Type 1 Diabetes Genetics Consortium. This consortium investigated children of European descent in Europe, North America, and Australia as well as 390 additional type 1 diabetes family trios from Canada.
KIAA0350 is known to be active almost exclusively in immune cells. Although scientists do not currently know the exact function of the protein the gene encodes, other research has predicted that it produces a protein called C-type lectin that is located on the surface of immune cells and binds to groups of sugars in the body.
“The role of KIAA0350 needs to be investigated,” says the study’s lead author, Hakon Hakonarson, M.D., Ph.D., the director of the Center for Applied Genomics at The Children’s Hospital. “However, a special cell type called a natural killer (NK) cell expresses this gene abundantly although at different levels based on these gene variants. Our hypothesis is that a special mutation in KIAA0350 may influence the sugar binding of the protein and trigger an autoimmune response that activates these NK cells in such a way that they attack and destroy the islet cells in the pancreas, resulting in type 1 diabetes. A particular version of the gene protects against this inappropriate autoimmune response, while a different version of the gene makes it more likely to happen. ”
The study appeared July 15 in an advance online letter in Nature.