Potential type 1 diabetes gene found

A new gene has been added to the list of determinants of type 1 diabetes following a genome-wide association (GWA) study by US and Canadian researchers.

Hakon Hakonarson and colleagues performed a GWA study on more than 500 patients with type 1 diabetes and more than 1,000 controls. As well as confirming associations with known type 1 diabetes-related genes, the team found a large linkage disequilibrium block on chromosome 16p13, which contains KIAA0350.

It is thought that the gene encodes a sugar-binding C-type lectin, a multi-talented group of proteins whose functions include carbohydrate recognition and cell adhesion.

The study also confirmed the known association with four other loci: the major histocompatibility complex (MHC), the insulin locus (INS), PTPN22 and CTLA4.

However, these four associations are thought responsible for just over half of the genetic risk for type 1 diabetes, "indicating that other loci exist", the authors write in the paper, published online this week in Nature

"Studies are underway to characterise the functional role of KIAA0350," the researchers, from The Children's Hospital of Philadelphia, the University of Pennsylvania and McGill, Manitoba and Ottawa universities in Canada, write.

"In light of the crucial role of the MHC genetic repertoire in antigen representation involving sugar groups, such as lectin, we hypothesise that a genetic variant in the binding site for such a molecule on the activating cytotoxic T-cell could elicit an auto-immune response that results in the destruction of the islet cells of the pancreas."

The researchers believe that the almost exclusive specificity of KIAA0350 in immune cells, including dendritic cells, B cells and natural killer cells, all of which are pivotal to the pathogenesis of type 1, indicates that it contributes to the disease by modulating immunity.

dx.doi.org/10.1038/nature06010