A team of scientists in the US and Canada have discovered a gene variant that is thought to increase a child’s risk for type 1 diabetes. The study is published in the advanced online publication of the journal Nature.
Type 1 diabetes used to be called juvenile diabetes because it mostly begins in childhood. It’s an autoimmune disease where the immune system destroys the insulin producing beta cells in the pancreas. Type 1 is fatal unless patients get frequent doses of insulin by injection to keep the body’s blood sugar under control.
More and more scientists are investigating the genetics of type 1 diabetes and the hope is this will lead to ways of preventing and treating the disease.
Senior author of the study, and director of Pediatric Endocrinology at McGill University, Dr Constantin Polychronakos said that it may one day be possible to predict which children are at high risk of type 1 diabetes by screening babies when they are born.
Since the unravelling of the human genome a few years ago, a new method called genome wide association (GWA) has emerged, where specialists in genetic research scan the DNA of patients and search over 500,000 genes for markers of disease.
In this study, pediatrics researchers at The Children’s Hospital of Philadelphia and McGill University in Montreal conducted such a search and discovered a new gene called KIAA0350 which sits on chromosome 16, that appears to play an important role in the development and maintenance of type 1 diabetes. They are carrying on with the project because they think this gene is only one of many that work together to wipe out the insulin producing cells. There could be as many as 15 or 20, they said in a prepared statement about their work.
Lead author of the study, director of the Center for Applied Genomics at The Children’s Hospital of Philadelphia, Dr Hakon Hakonarson said:
“The genotyping technology we now have available has revolutionized the way we can ask and answer research questions.”
“Unlike the previous technology, which was quite limited and dealt largely with relatively rare gene variants, we can now detect common genetic variants that are important in large numbers of individuals, and begin to understand how multiple genes interact in complex diseases such as diabetes,” added Hakonarson.
Hakonarson and colleagues scanned the genomes of 1,046 children with type 1 diabetes. They had access to DNA samples of patients and their families attending pediatric diabetes clinics in Philadelphia in the US, and four cities in Canada.
They then compared the genomes of 563 type 1 diabetes patients with those of 1,146 matched controls (children without the disease). The results were combined with those from another indepedent search of 483 children and both parents, where the genomes of all three family members were scanned in each case.
The scientists found four locations where genes linked to type 1 diabetes were already known to exist. But they also discovered a new locus on chromosome 16, occupied by KIAA0350. They verified their results by repeating the analysis on a cohort of 1,333 children with type 1 from the Type 1 Diabetes Genetics Consortium and another 390 family trios based in Canada. The Type 1 Diabetes Genetics Consortium includes children of European descent in Europe, North America and Australia.
Scientists already know that KIAA0350 plays an important role in immune cells, but what they don’t know exactly is what the protein that the gene encodes does. Some research suggests the gene codes for a protein called C-type lectin that binds to sugars and lives on the surface of immune cells.
Hakonarson emphasized that KIAA0350 has to be investigated to find out exactly what it does. He said that scientists know that natural killer cells (NKs) express this gene, some more abundantly than others depending on the gene variant.
“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,” explained Hakonarson.
The researchers said their hunch is that one variant of the gene encourages the destruction of the pancreatic insulin producing cells, while another variant stops it.
The GWA scan for this study was done at the Children’s Hospital of Philadelphia’s Center for Applied Genomics which has the highly automated analytic equipment that enables rapid scanning of a patient’s DNA. The equipment shows the scanned patient’s genotype; it specifies each variant of each of the patient’s 30,000 genes.
Other projects going on at the Center include finding genes linked to childhood asthma, allergy, inflammatory bowel disease, hypertension, juvenile rheumatoid arthritis, obesity, attention-deficit hyperactivity disorder, autism, and the pediatric cancer neuroblastoma.
“A genome-wide association study identifies KIAA0350 as a type 1 diabetes gene.”
Hakon Hakonarson, Struan F. A. Grant, Jonathan P. Bradfield, Luc Marchand, Cecilia E. Kim, Joseph T. Glessner, Rosemarie Grabs, Tracy Casalunovo, Shayne P. Taback, Edward C. Frackelton, Margaret L. Lawson, Luke J. Robinson, Robert Skraban, Yang Lu, Rosetta M. Chiavacci, Charles A. Stanley, Susan E. Kirsch, Eric F. Rappaport, Jordan S. Orange, Dimitri S. Monos, Marcella Devoto, Hui-Qi Qu NS Constantin Polychronakos.
Nature: Published online 15 July 2007.
doi:10.1038/nature06010
Written by: Catharine Paddock
Writer: Medical News Today