In a large-scale study conducted with 2,643 children, international researchers with the participation of the Department of Experimental Pneumology of Ruhr-University Bochum (RUB), Germany (Prof. Dr. Albrecht Bufe), have discovered a gene variant that contributes significantly to the risk of childhood asthma.
Comparisons of the entire genome of healthy children and those afflicted with asthma (genome wide screening) drew their attention to variants of a sequence in on Chromosome 17q21 which encodes the ORMDL3 protein group. Variants in this gene sequence are linked to a significantly higher risk of asthma. The researchers have reported on their findings in the current online issue of the science magazine, Nature.
Environmental factors are the trigger
Bronchial asthma is one of the most common chronic childhood lung diseases. Some 15% of German children between the age of 6 and 16 are victims of the disease, while up to 30% of children in Australia, England and the USA are affected. Asthma is an inflammatory reaction of the bronchial mucosa which leads to restriction of the respiratory passages resulting in shortness of breath, coughing, wheezing and a notable impairment to the quality of life coupled with chronic changes in the lung. Allergies to harmless environmental substances such as grass, tree pollen and house dust mites trigger asthma in 80% of children's cases. These allergies as well as infections and environmental conditions function in a way that is as yet not fully understood as triggering factors, leading to the outbreak of the disease.
Genes lay the foundation
One of the causes for the appearance of asthma is certain hereditary factors: 70 percent of children whose parents both suffer from asthma are also likely to get the disease. A child with healthy parents has only a five to 15-percent risk, depending on where it grows up. Genetic factors include variations in the complex regulation of the sensitisation to allergies, variations in the reaction of the innate immune system to innumerable microbial and other environmental factors and variations in genes responsible for inflammatory reactions in mucous membranes and the immune system. "Numerous gene variations in the broadest variety of genes are responsible for the emergence of allergies and allergic diseases such as neurodermatitis, hay fever and indeed asthma", explains Prof. Bufe. "However, an unambiguous clarification of this complex situation has only been partially possible up to now."
Searching for stars in the sky
To gain deeper insight, Bochum's Experimental Pneumology Dept. is participating in the "Multicentre Asthma Genetics in Childhood Study" (MAGICS, directed by the University of Munich Children's Hospital, PD Dr. M. Kabesch). This network is the source of most of the 2,643 children examined for the analysis published in NATURE (321 asthmatics and healthy children come from Bochum). "One reason for the special significance of this study is the very large number of children examined", says Prof. Bufe. "The other is that for the first time, the 'genome wide screening' method was applied to such a large group of patients." The process involves comparing all of the genetic information of all the test persons with that of the others. Variations in the genes - for instance, the exchange of individual bases, which occurs frequently and which by no means has to inevitably result in illness - are examined for whether they often appear together with a specific disease. "With some 40,000 human genes, this is like searching for stars in the sky", illustrates Prof. Bufe.
The function of the gene sequence remains unclear