Scientists have identified over 30 genes that drastically affect an antibody that is involved in allergies and asthma.
According to the researchers from Canada, the UK, Sweden and the US, found that the genes are concentrated in eosinophils, a white cell that ignites inflammation in asthmatic airways. The genes indicate when the eosinophils are activated and primed to cause the most damage.
The research team used a novel technique, known as an "epigenome-wide association study," to discover these genes. Epigenetic changes to DNA do not alter the underlying sequence of the genetic code, but can still be passed on as cells divide. They program the cells to form specialized types and tissues.
Mark Lathrop, Scientific Director of the McGill University and Genome Quebec Innovation Centre and a co-leader of the new study, said that in their study, they have shown that certain epigenomic modifications contribute to atopic diseases such as allergy and asthma. This new knowledge points the way to multiple novel molecular pathways that could be explored for their usefulness as therapeutic targets.
Epigenetic changes are most easily detected by alterations in methyl molecules that are attached at the side of the DNA chain. The researchers therefore concentrated on methylation hotspots known as CpG islands that are positioned near many genes. They tested whether methylation levels in these islands in white cells from individuals with and without asthma were correlated with the level of the IgE in the blood. They found strong associations between IgE and CpG island methylation at 36 places in 34 genes. In asthma sufferers, these genes produce more IgE, contributing to asthma symptoms.
Some of the IgE-related genes were known to be present in eosinophil cells. The researchers therefore separated eosinophils from the blood of 24 subjects and showed all 34 genes to have their strongest effects in asthmatics with high IgE levels. White blood cells from asthmatic families in the Saguenay-Lac-Saint-Jean region of Quebec were used to test the validity of analyses of samples of families in the UK.
The study is published online in Nature.
