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New genetic markers for diabetes-related traits uncovered

25 January 2010
Appeared in BioNews 542

An international team of 174 research centres has identified 13 new gene variants associated with blood glucose and insulin, with five linked to Type-2 diabetes. The findings - published last week in the journal Nature Genetics -raise hopes of better treatments for the condition.

The Meta-Analyses of Glucose and Insulin Related Traits Consortium (MAGIC) studied the genomes and blood glucose levels of more than 100,000 people of European descent. The new findings are published in two papers - one identifying ten new gene variants and the second three more. Dr Jim Wilson, a geneticist from Edinburgh University and a member of the team, told The Times newspaper: 'This is an incredibly important finding. The discovery of these new genes influencing blood-sugar levels is the first step on the important journey to developing new therapies for diabetes'.

The first study looked for genes influencing metabolism, such as fasting glucose and insulin levels. Researchers analysed 2.5 million genetic variants in 21 genome-wide association studies (GWAS). GWAS look for genetic variants linked to diseases and traits. The chances of finding variants subtly associated with a disease is increased by studying thousands of genomes.

The study identified five variants linked to Type-2 diabetes. Most affected insulin release by beta cells and not the body's response to insulin levels. This suggests beta cell impairment may have a larger role in Type-2 diabetes than previously believed, according to the study authors.

'The hallmarks of Type-2 diabetes are insulin resistance and impaired beta cell', study's lead author Dr Inês Barroso from the UK's Wellcome Trust Sanger Institute in Cambridge said in Science Daily. 'We were intrigued to find that most of the newly found variants influence insulin secretion rather than insulin resistance. Only one variant, near IGF1, is associated with insulin resistance'.

The second paper found a gene variant that impairs beta cell functioning by analysing 15,000 genomes in nine GWAS. The risk variant in GIPR, a gene that codes for a beta cell-regulating hormone, affected glucose levels two hours after a sugary meal.

The findings highlight the role of 'incretin' hormones, released from endocrine cells in the gut. 'This finding adds to a growing body of evidence implicating the incretin pathways in Type-2 diabetes risk. These pathways, which stimulate insulin secretion in response to digestion of food, may offer a potential avenue for therapeutic intervention', said senior author Dr Richard Watanabe, from the University of Southern California.

Further research is needed to identify other gene variants and to confirm that these variants are also found in non-Europeans. 'Even with the discovery of these variants, we've only explained about 10 per cent of the genetic contribution to fasting glucose in people who do not have diabetes', said Dr Jose Florez from Massachusetts General Hospital and Harvard Medical School who is lead co-author on the first study.

Diabetes affects more than 220 million people worldwide. Over 90 per cent of these cases are caused by Type-2 diabetes, where cells fail to recognise and react to insulin, triggering abnormally high levels of glucose in the blood. Type-2 diabetes is also referred to as late-onset diabetes because it typically develops later in life.

Diabetes gene points way to new treatments
The Times |  18 January 2010
Genetics of diabetes reveals biology but does not improve prediction
PHG Foundation |  19 January 2010
New gene variants associated with glucose, insulin levels, some with diabetes risk
ScienceDaily |  18 January 2010
Researchers uncover novel genetic markers for diabetes-related traits
Wellcome Trust |  18 January 2010
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