Asthma gene discovery provides new insight
Researchers have discovered a gene variant that contributes significantly to the risk of childhood asthma. The findings are the culmination of a study conducted with almost 3 000 children, that compared the entire genome of healthy children with those of children afflicted with asthma. This genome-wide screening (the first ever of such a large group) identified variants of a sequence on Chromosome 17q21 which encodes the ORMDL3 protein group. With 30% of children in Australia, England and the United States alone, being victims of the disease, the discovery signals new hope in preventing asthma worldwide.
'Asthma is the major chronic childhood illness in Europe, costing the European Community more than EUR 3 billion each year,' says Imperial College Londonís Professor Bill Cookson. 'Although effective therapies for mild asthma exist, the 10% of children with severe disease account for 60% of this expense, and even when treatment is effective, it is not able to cure the disease.'
|A total of 70% of children whose
parents both suffer from asthma are also likely to get the disease. Understanding
the genetic and environmental causes of asthma is a priority of research
centres across Europe.
Prof. Cookson is coordinator of GABRIEL, a multidisciplinary study aimed at identifying the genetic and environmental causes of asthma in Europe, funded under the 6th Research Framework Programme. The large-scale screening was conducted within the projectís framework, with the participation of Professor Albrecht Bufe and the Department of Experimental Pneumology of Ruhr-University Bochum.
The screening of 2 643 children (sourced with the assistance of the Multicentre Asthma Genetics in Childhood Study) identified a suspicious sequence on Chromosome 17q21, variations of which appeared with slightly greater frequency in children suffering from asthma ó this indicates a clear risk factor. The function of the gene complex remains unknown. 'We only know that ORMDL3 expression is prominent in many cells and tissues, especially in immune cells,' says Prof. Bufe.
'Here we have found something that is completely unknown, completely new ó this might open up a brand new perspective of our understanding of childrenís asthma,' he says. The next step for researchers is to discover the precise function of the ORMDL3 proteins affected by variations in the gene complex.
In addition to the certain hereditary factors that account for the appearance of asthma, environmental factors are also triggers of the disease. In fact, in 80% of cases, allergies to grass, tree pollen, house dust mites and other harmless environmental matter set off a childís asthma. As triggering factors, unfortunately, these allergies (as well as infections and environmental conditions) function in a way that is yet to be fully understood.
Since asthma is not exclusively dependent on genes, and is caused instead by
environmental stimuli, genetically predisposed children do not necessarily have
to become ill. According to a workgroup coordinated by Munich Universityís Childrenís
Clinic with the participation of Bochumís Department of Experimental Pneumology,
risk of asthma can be reduced by training the immune system in the first year
In the long term, researchers aim to identify the factors (as well as understand the mechanisms) that contribute to the immune systemís tolerance to allergies and asthma in childhood. 'In this regard,' notes Prof. Bufe, 'the genetic variations apparently play an important role.'
Medical Faculty of Ruhr-University Bochum