Scientists Find New Genetic Explanation For Type 2 Diabetes

An international team of scientists has found four points on the human gene map that together account for 70 per cent of the genetic predisposition to type 2 diabetes.

Type 2 diabetes mellitus is caused by a combination of environmental and genetic factors, of which very little is known.

However, a new technology called "high density micro-arrays" allows researchers to profile genetic maps in a detailed and precise way. They can investigate the different ways that individual points on the human gene map are expressed in different people.

A point on the gene map is called a nucleotide. About 1 in every 600 nucleotides has a mutant variation. Geneticists talk of testing SNPs - single nucleotide polymorphisms - literally looking for the different mutant forms of nucleotides.

By looking at the different mutant forms of nucleotides (the SNPs) it is possible to find the forms that are prevalent among people who have a disease and compare them to the forms that are prevalent among those that do not have the disease.

In this, the scientists tested 392,935 SNPs in a case control cohort of 1,400 French people - comprising 700 people with type 2 diabetes and another 700 free of the disease.

They then took the DNA sequences that showed the most frequent differences between the two groups and tested them in a second cohort of 5,000 people.

After this second test the scientists were able to identify four points ("loci") on the gene map that when expressed as particular variants, confer type 2 diabetes risk. They also confirmed a link with a gene called TCF7L2, which has been found before.

One of the four loci found in the people with type 2 diabetes is a mutant form of a zinc transporter called SLC30A8, which helps to control the secretion of insulin. People with type 2 diabetes either don't make enough insulin or they have developed reduced sensitivity to insulin, resulting in excess blood sugar. The other loci were also linked to insulin regulation.

The main conclusion of the study is that it demonstrates the important contribution that a genome-wide approach can make to the understanding of a disease.

Professor Philippe Froguel, of the Division of Medicine at Imperial College London, and one of the researchers on the project said, "If we can tell someone that their genetics mean they are pre-disposed towards type-2 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-2 diabetes to develop better treatments."

Diabetes UK, a national charity, estimates that 2 million people in the UK have diabetes, of which 75 per cent have type 2. They also think that about three quarters of a million other people have diabetes but don't realize it.