Scientists find genes linked to diabetes

[Al-khiyal]

Scientists find genes linked to diabetes

March 31, 2008 -- Scientists have found six new genes linked to type 2 diabetes, a discovery that will improve understanding of how the disease develops.

Each of the disease variants of the genes raises the risk of developing diabetes by only a small amount, but scientists say the combined impact of the collection of genes could be powerful, and the discovery could help develop new forms of prevention and treatment. One of the genes has also been linked to prostate cancer.

Diabetes occurs when the body cannot regulate its blood sugar levels. It is thought to affect more than 2 million people in the UK and another 750,000 are unaware of their condition. In type 2 diabetes, which is associated with obesity and is the more common form of the disease, the body does not respond properly to insulin produced by beta cells in the pancreas, which also may be making less of the hormone.

In the study, published yesterday in Nature Genetics, 90 researchers from more than 40 European and US centres pooled genetic data gathered from more than 90,000 people. "The sort of studies we're doing are designed to pick up common variants," said Mark McCarthy of the University of Oxford, who led the research. "Across these six, some of the variants are in 10% [of the population], in other cases the one that's increasing the risk is the majority version that is in 90%."

McCarthy said inheriting a disease variant of any of the genes from either parent could increase a person's risk of developing type 2 diabetes by 10%-15%. "There'll be a few individuals who will have many of these risk variants and they'll have higher risk of diabetes than individuals who have been lucky enough to end up with very few."

Since none of the new genes were previously suspected of having a role in diabetes, there is still much work to do in working out what the genes are responsible for, though there are clues. "Virtually all of the genes [found so far] seem to be impacting on the ability of the beta cells to compensate for insulin resistance," he said.

He added that a particular surprise was that one of the genes found linked to type 2 diabetes was recently shown to play a role in prostate cancer. "One of the most exciting bits of this field is that we're finding lots of unexpected connections that sometimes genes seem to influence diseases that we hadn't previously thought of as connected."

Simon Howell, chairman of Diabetes UK, said: "It's remarkable that we still know so little about such a major condition as type 2 diabetes. By revealing new pathways by which the body normally keeps blood glucose levels under control, this research offers new opportunities for more effective ways of treating and preventing this condition."

The findings are the latest success in a relatively recent technique called the genome-wide association study.

A decade ago, genetics research usually involved looking in families with rare conditions, such as cystic fibrosis, to find rare single gene mutations that had big effects. But after the human genome project in 2000, which mapped every gene in the body, and subsequent improvements in screening technology, scientists are now able to carry out large-scale comparisons of huge numbers of people.

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Six new genes associated with type 2 diabetes discovered, including one with role in prostate cancer

March 31, 2008 -- Scientists have identified six new genes which play a role in the development of type 2 diabetes, and among the group is the second gene known to also play a role in prostate cancer.

The new findings bring the total number of genes or genomic regions implicated in diabetes to 16, said Laura Scott, assistant research scientist in the Department of Biostatistics. Researchers from the University of Michigan were one of three teams of scientists in Europe and North America that led the multi-group collaboration. The findings, which were published March 30 in the journal Nature Genetics, provide new insights into the mechanisms which are usually responsible for the control of glucose, or sugar, levels in the blood, and to the derangements that can result in type 2 diabetes, which impacts more than 170 million people worldwide.

One of the newly discovered genes, which goes by the name of JAZF1, contains a separate variant that has recently been shown to play a role in prostate cancer, and is the second gene that appears to play a role in both conditions. The first identified overlap between genes for prostate cancer and type 2 diabetes was with HNF1B, which is also involved in an early onset form of diabetes discovered at U-M in an unrelated study, called Maturity Onset Diabetes of the Young (MODY). In HNF1B, the same variant that is associated with increased risk of diabetes is associated with decreased risk of prostate cancer. In JAZF1, the diabetes and prostate cancer variants reside in different parts of the gene and there is no known relationship between them.

"Genetic studies of this kind are revealing new and unsuspected connections between diseases," says Dr Eleftheria Zeggini from the University of Oxford, first author on the paper. "This is now the second example of a gene which affects both type 2 diabetes and prostate cancer. We don't yet know what the connections are, but this has important implications for the future design of drugs for these conditions".

"Some of these genes for type 2 diabetes might be involved in diseases other than prostate cancer, in fact there is already a known overlap with heart disease in another genomic region" Scott said. "We have about 25,000 genes, and we've found a very small number by genome wide studies, so to have the same genomic regions come up in studies of different diseases is actually pretty interesting."

Type 2 diabetes is characterized by high levels of blood sugar, caused by the body's inability to utilize insulin to move blood sugar into the cells for energy. Type 2 diabetes affects nearly 21 million in the United States and the incidence of the disease has skyrocketed in the last 30 years. Diabetes is a major cause of heart disease and stroke, as well as the most common cause of blindness, kidney failure and amputations in U.S. adults.

"The remarkable recent progress in identifying regions of the genome that increase risk to diabetes - from 3 to 16 in only a year - will help us unravel the complex basis diabetes and may suggest new and better tailored methods to prevent or treat this disease.," said U-M's Michael Boehnke, the lead scientist on the Finland-United States Investigation of Non-Insulin-Dependent Diabetes Mellitus Genetics (FUSION) study group, one of the three lead groups in the study.

The researchers in this project set out to find differences in the genetic code that contribute to individual differences in susceptibility to disease. Previous efforts from these groups and others identified ten genes contributing to type 2 diabetes risk.

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Genetic variants may be ‘trading’ one illness with another using new genes, Oxford research shows

March 31, 2008 -- A genetic trade-off between type 2 diabetes and prostate cancer has been identified by scientists with the discovery of genes that can raise the risk of one condition while protecting against the other.

The research has suggested that the two very different diseases may be influenced by the same biological pathway. It should improve understanding of both type 2, the adult-onset form of diabetes, and prostate tumours. This should help scientists to avoid designing drugs aimed at one disorder that inadvertently trigger the other.

The trade-off emerged from an international search for genetic influences on type 2 diabetes, which has linked six new genes to the condition. One of these is a gene called JAZF1: people who carry one copy of a particular variant are about 15 per cent more likely than usual to develop diabetes. Those with two copies have a 30 per cent increased risk. A different variant of JAZF1, however, is also known to raise the risk of prostate cancer. Research indicates that a raised risk of one disorder is probably balanced by a lower risk of the other.

The findings are significant because another gene that has opposing effects on the two diseases, called TCF2, was identified last year. A third, CDKN2A, appears to raise the risk of type 2 diabetes when overactive, while raising the risk of cancer, particularly malignant melanoma, when underactive.

Mark McCarthy, Professor of Diabetes at the University of Oxford and a leader of the JAZF1 study, said that while one “seesaw” gene could be a fluke, the discovery of three makes it more likely that there is interaction.

His Oxford colleague Eleftheria Zeggini, the first author of a Nature Genetics paper that describes JAZF1 and the five other diabetes genes, said: “Genetic studies of this kind are revealing new and unsuspected connections between diseases. We don’t yet know what the connections are, but this has important implications for the future design of drugs for these conditions.”

Professor McCarthy said that the key to understanding the link probably lay in the causes of diabetes and cancer. Type 2 diabetes occurs when cells become resistant to insulin, and the pancreas cannot produce enough to cope because the beta cells that make it lose the ability to regenerate. This leads to elevated blood sugar. Cancer occurs when cells divide unchecked, causing tumours to grow.

Genetic variants that speed up cell division seem to help diabetes, because they allow beta cells to regenerate and make more insulin, but also promote cancer. Those that slow it down have the opposite effect. Professor McCarthy said: “Put bluntly, too great a tendency for cell cycle and cell division would tend to predispose to cancer, and too little towards diabetes.”

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Évolution de la maladie :
Découverte de six gènes liés au diabète de type 2

Mardi 1 Avril 2008 -- Six gènes liés au diabète de type 2 devant aider à comprendre l’évolution de la maladie ont été découverts par des scientifiques venant de dizaines de centres de recherche en Europe et aux États-Unis, a révélé une étude publiée hier dans le magazine britannique spécialisé Nature Genetics. Cette découverte offre de nouvelles opportunités pour le développement de traitements plus efficaces et de moyens de prévention du diabète. Dans leur étude, les chercheurs européens et américains ont essayé d’identifier les variantes communes de la maladie chez 90 000 personnes. “Ces variantes existent chez 10% de la population”, indique l’un des chercheurs, le docteur Mark McCarthy, de l’université britannique d’Oxford, ajoutant que “toute variante héritée du père ou de la mère augmente de 10 à 15% le risque de développer un diabète de type 2”. D’après ce chercheur, pratiquement tous les six gènes identifiés jusqu’à présent semblent avoir un impact sur la capacité des cellules bêta de compenser l’insuffisance de l’insuline dans le sang. L’étude a, par ailleurs, montré que l’un des gènes liés au diabète de type 2 joue un rôle dans le développement du cancer de la prostate, a souligné le médecin.