Harmful blood glucose levels linked to defective gene
May 1, 2008 - 4:00:00 AM
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There are mutations, known as single-nucleotide polymorphisms, in around
one in every 600 nucleotides. The scientists examined over 392,000 of
these mutations to find the ones specific to high blood glucose levels.
The researchers confirmed their findings by analysing the genetic makeup
of a further 8000 individuals with blood glucose levels within the non
diabetic range, to verify that the same genetic mutations were visible
in these individuals.
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By Imperial College London,
[RxPG]
A genetic mutation that can raise the amount of glucose in a person's
blood to harmful levels is identified today in a study in the journal
Science.
High levels of blood glucose increase the risk of cardiovascular disease
and early death, even in healthy people who do not have diabetes and
whose blood glucose levels are at the higher end of the range considered
'normal' by doctors. One in five people in the UK has a high blood
glucose level.
The study, by researchers from Imperial College London, the French
National Research Institute and McGill University in Canada, reveals an
association between high levels of blood glucose and a mutation in a
gene known as G6PC2 or IGRP.
The research shows that the mutated IGRP gene blocks the action of a
sensor called glucokinase. By stopping glucokinase from doing its job,
the gene prevents the body from keeping tight control over its levels of
blood glucose. Glucokinase works by signalling to cells known as beta
cells which then secrete insulin to keep blood glucose levels under
control.
The researchers hope their findings could enable a therapy to be
developed to stop the defective IGRP gene from blocking the glucokinase
sensor. This would restore control of glucose levels in the blood and
help prevent these levels from becoming too high.
The researchers believe that the mutation in the IGRP gene could cause
an increase of around five percent in the level of glucose in the blood.
This small percentage increase would be enough to raise a person's risk
of health problems because levels of blood glucose are so tightly
controlled.
Epidemiological studies have shown that 80 percent of the risk of
cardiovascular disease is related to a blood glucose level just above
the average. High blood glucose levels are linked to obesity, poor
nutrition and lack of exercise.
Professor Philippe Froguel, leading author of the research from the
French National Research Institute and the Department of Genomic
Medicine at Imperial College London, said: Having a high level of blood
glucose is a bit like having high cholesterol or high blood pressure in
that the higher the level, the greater your risk of serious health
problems. Our study helps unravel the genetic reasons why some people
have higher levels of glucose in their blood than others.
At present, doctors advise people with high blood glucose levels to
lose weight and exercise. We hope that ultimately our research will mean
we can develop new treatments to stop people from developing high blood
glucose levels, which would enable them to live longer and healthier
lives, added Professor Froguel.
The scientists reached their conclusions after comparing the genetic
makeup of 654 non diabetic people with differing levels of blood
glucose, from the low to the high end of the 'normal' range. The
researchers looked at mutations in the building blocks, called
nucleotides, which make up DNA.
There are mutations, known as single-nucleotide polymorphisms, in around
one in every 600 nucleotides. The scientists examined over 392,000 of
these mutations to find the ones specific to high blood glucose levels.
The researchers confirmed their findings by analysing the genetic makeup
of a further 8000 individuals with blood glucose levels within the non
diabetic range, to verify that the same genetic mutations were visible
in these individuals.
Today's study follows on from a study published in February 2007 by the
same team, where they identified the most important genes associated
with a risk of developing type-2 diabetes.
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