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Scientists have discovered over 30 new genes that
predispose people to allergies and asthma, some of
which could be targets for new drugs.
This new study, published in Nature and led by
scientists at Imperial College London, has taken 10
years involving researchers in the UK, US, Canada
and Sweden, who have used new ways to study the
genes in the immune system.
This new study, published in Nature and led by
scientists at Imperial College London, has taken 10
years involving researchers in the UK, US, Canada
and Sweden, who have used new ways to study the
genes in the immune system.
The team looked at epigenetic changes, which do not
affect the genetic code itself but which influence
the activity of genes.
Using this approach, the researchers were able to
pinpoint genes that regulate a particular antibody
that is involved in triggering allergic responses.
This antibody, called immunoglobin E (IgE), was
known to researchers already but before today's
study scientists had been unable to identify which
genes regulate its activities.
The new study turned to epigenetics to look for new
therapeutic targets. Genes can be rendered inactive
by attaching methyl molecules to the DNA, a process
called methylation.
The researchers analysed white blood cells from
families with asthma in the UK to see whether
methylation levels in certain parts of the genome
were correlated with the level of IgE in the blood.
To be sure of their results, the researchers tested
whether they held true in additional volunteers with
high and low levels of IgE from Wales and further
asthmatic families from Quebec.
They found strong associations between IgE and low
methylation at 36 places in 34 genes. In people with
asthma, these genes are overactive, making them
produce more IgE which contributes to asthma
symptoms.
Some of the IgE-related genes were known to encode
proteins produced by eosinophils, a type of white
blood cell that promotes inflammation in asthma
sufferers' airways. The researchers believe these
genes may activate the eosinophils, priming them to
cause the most damage.
To test this idea, they isolated eosinophils from
the blood of 24 subjects and showed that all 34
genes are most active in asthmatics with high IgE
levels.
Therapies that neutralise eosinophils already exist,
but they are very expensive and only effective in
some asthmatics. The newly found activation signals
provide a possible means of identifying which
patients will respond before starting therapy.
The study was led by Professor William Cookson and
Professor Miriam Moffatt from the National Heart &
Lung Institute at Imperial College London.
The Freemasons' Grand Charity, the Wellcome Trust
and grants from the Québec Government provided the
principal funding for the study.
For more information
L. Liang et al. 'An
epigenome-wide association study of total serum
immunoglobulin E concentration.'
Nature, 2015.
doi:10.1038/nature14125
Imperial College London
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