Research: GENETIC RISK FACTORS FOR TYPE 2 DIABETES27 April 2007 |
UK researchers have identified variants in three genes that predispose people to type 2 diabetes.
The researchers at the University of Oxford and the Peninsula Medical School, Exeter, found the genes by comparing the genomes of 2000 people with type 2 diabetes with those of 3000 'controls'.
The study was part of the Wellcome Trust Case Control Consortium, which is searching for genetic variations that may predispose people to or protect them from major diseases.
The initial findings were then confirmed by studying a further 9000 samples from the UK (the majority of them from the Dundee area, collected by researchers from the Ninewells Hospital and Medical School).
The three genes identified are called IGF2BP2, CDKAL1 and CDKN2A/CDKN2B. For each of the genes, the researchers found that two variants are common in the population, one of which is associated with an increased risk of developing type 2 diabetes and the other with reduced risk. Each high-risk version increases the risk of type 2 diabetes by between 10 and 20 per cent.
The exact role of the genes implicated by these studies is still uncertain. However, two of them appear to be involved in the development, function and regeneration of insulin-producing beta cells in the pancreas.
This finding is likely to help to answer a long-standing controversy in the diabetes field, concerning the extent to which a reduced number of pancreatic beta cells (as opposed to reduced function) contributes to the development of diabetes.
Type 2 diabetes occurs as a result of the body's failure to produce enough insulin to maintain normal levels of glucose (sugar) in the blood. This failure is usually compounded by a reduction in the capacity of the insulin released to work properly in tissues such as muscle and fat (known as insulin resistance). It is a major cause of heart disease and stroke, as well as blindness and kidney failure.
The research was conducted in collaboration with two other groups from the USA and Scandinavia, who were undertaking similar research studies in samples from Sweden and Finland. Their results, which identified the same three genes, were published alongside the UK study. In a unique collaboration, these three international groups chose to combine forces rather than compete, resulting in the largest ever collaborative study of type 2 diabetes, involving over 32 000 subjects.
The findings, published in the journal Science, bring the total number of genes linked to type 2 diabetes to nine, including the FTO gene reported by the same UK group two weeks ago. The FTO gene influences individual risk of type 2 diabetes through its effect on weight and obesity.
See also
- Press release (27 April 2007)
- Research: Clear genetic link to obesity found (13 April 2007)
- Zeggini E et al. Replication of genome-wide association signals in UK reveals risk loci for type 2 diabetes. Science 2007 [epub ahead of print].