Scientists have mapped the most important genes associated with the risk of developing Type II diabetes, bringing a genetic test to identify those most at risk a step closer.
Researchers have identified five loci, or locations on peoples' genetic maps that correspond to a risk of developing this life threatening disorder. The genetic mutations were found after scanning nearly 400,000 mutations in nearly 6,500 people.
AdvertisementThe scientists from various international institutions believe their findings explain up to 70 per cent of the genetic background of Type II diabetes - a diseases that affects over 1.9m people in the UK and is characterised by either low levels of, or an inadequate response to insulin - a hormone secreted by the pancreas to release energy from the breakdown of carbohydrates.
The disease is frequently passed from generation to generation, and its rapidly increasing prevalence is thought to be due to environmental factors, such as increased availability of food and decreased necessity for exercise, acting on genetically susceptible individuals.
Professor Philippe Froguel, one of the authors of the article published in Nature from the Division of Medicine at Imperial College London, said: "The two major reasons why people develop Type II diabetes are obesity and a family link. Our new findings mean that we can create a good genetic test to predict people's risk of developing this type of diabetes."
"If we can tell someone that their genetics mean they are pre-disposed towards Type II diabetes, they will be much more motivated to change things such as their diet to reduce their chances of developing the disorder. We can also use what we know about the specific genetic mutations associated with Type II diabetes to develop better treatments."
The researchers used two single nucleotide polymorphism (SNP) comparative genomic hybridization (CGH) platforms for identifying the gene mutations; Illumina's Infinium Human1 and Human Hap300 Beadarrays.
The study confirmed the association of mutated TCF7L2 genes with an increased risk of developing the disease, as well as identifying four other gene mutations that are also implicated in increased risk of disease development.
The most significant of the new genes identified was SLC30A8, which encodes a zinc transporter expressed solely by the secretory vesicles of beta-cells. This gene is implicated in the final stages of insulin biosynthesis, which involve the co-crystallisation with zinc. Notably, the over-expression of the SLC30A8 gene in insulinoma cells (pancreatic endocrine cancer cells) increases glucose-stimulated insulin secretion leading to hypoglyceamia.
Two significant mutations, rs1111875 and rs7923837, were located near the telomeric end of chromosome 10 which contains two genes of known biological significance, the insulin degrading enzyme (IDE) and the homeodomain protein HHEX as well as the kinesin-interacting factor 11(KIF11).
HHEX is essential for the development of the pancreas and liver and is a target of the Wnt signaling pathway, as is TCF7L2.
Two previous studies into the role of IDE in the onset of Type II diabetes indicated a weak association, which was not confirmed by a third study. Further mapping of the IDE-KIF11-HHEX loci in different populations as well as biological studies will be needed to identify the causative variant.
Two further loci were found in the study; the first located in the introns of exostosin 2 (EXT2), which modulates hedgehog signaling, early pancreatic development and insulin synthesis.
The second is located in chromosome 11, mapped to a linkage disequilibrium block that contains the hypothetical LOC387761 gene.
Professor David Balding, co-author of the study from Imperial's Division of Epidemiology, Public Health and Primary Care, said: "Until now, progress in understanding how genes influence disease has been painfully slow. This study is one of the first large studies to report results using the new genome-wide technology that governments and research charities have invested heavily in during the past few years."
"Our research shows that this technology can generate big leaps forward. The task now is to study the genes identified in our work more intensively, to understand more fully the disease processes involved, devise therapies for those affected and to try to prevent future cases."
Source: Bio-Bio Technology
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