Paediatric researchers have made a key breakthrough in the battle against diabetes by mapping an important gene that puts children at risk of Type 1 diabetes.
A faulty gene on Chromosome 16 boosts the risk of developing Type 1 diabetes, also called juvenile or childhood diabetes as it often occurs in young patients, according to the latest study into the causes of this disease.
Three variants of a gene called KIAA0350 were spotted as risk factors in a genetic profiling of 563 patients with Type 1 diabetes, which were compared to 1,146 healthy people, says the study published online by Nature.
Type 1 diabetes occurs when the immune system destroys cells in the pancreas that produce insulin, the hormone that regulates blood glucose.
The research led by Hakon Hakonarson, the director of the Center for Applied Genomics at The Children's Hospital of Philadelphia, adds to the list of suspected genes, spotted on Chromosomes 6, 11, 1 and 2, each of which appear to play different roles in the disease.
As investigators continue to pinpoint genes contributing to diabetes, they have their eyes on providing a scientific basis for designing better treatments and preventive measures for the disease.
As the project continues, the study team expects to identify additional genes thought to interact with each other in the disease.
"The genotyping technology which is available has revolutionised the way we can ask and answer research questions," said Hakonarson.
The researchers confirmed the four previously identified locations for genes contributing to Type 1 diabetes, 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 with the disease from the Type 1 Diabetes Genetics Consortium, which includes children from European descent in Europe, North America and Australia, as well as in 390 additional type 1 diabetes family trios from Canada.
Constantin Polychronakos, director of Pediatric Endocrinology at McGill University and senior author of the study, said that better knowledge of genes that predispose to Type 1 diabetes may later enable physicians to screen newborns to predict those at high risk for the disease.
The gene implicated in the current research, 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, said Hakonarson. However, a special cell type called a natural killer 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 auto-immune 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," he said.
A particular version of the gene protects against this inappropriate auto-immune response, while a different version of the gene makes it more likely to happen.
Although much research remains to be done, better understanding of the disease may guide doctors to new and improved therapies.
"If we know the gene pathways that give rise to Type 1 diabetes, we hope to intervene early in life with targeted drugs or cell therapies to prevent the disease from developing," said Polychronakos.
The current research used a technique called 'genome-wide association', in which highly automated analytic equipment rapidly scans each patient's DNA for more than half a million genetic markers.
It was performed at the Center for Applied Genomics at Children's Hospital. The Center's tools spell out a patient's genotype, the specific pattern of variations among an individual's 30,000 genes.
"This study is the first one that our centre has published on a gene associated with a complex childhood disease, but we have many projects under way and several other papers in press," said Hakonarson.