Genetic of Asthma and Allergy

Summary

Sennertus (1850) first commented that his wife , three of her sibs and a niece all suffered from asthma . Salter in 1860 states “is asthma .

Hereditary ? “ It seems that there can be not doubt  that it is . Beside the number of cases in which there is a family history of asthma is greater than will be found by chance.

On the other hand the recent reports shows an increase of asthma and allergy cases in developing countries , specially in children , although there is an improvement of medication and treatment . But the rate of mortality is increasing too.

Considering the development of genetic and immunology during recent years , and the genetic predisposition of different diseases . It seems that different factors, especially genetic predisposition play an important role on development of asthma and allergy . It seems that several genas are involved in the development of asthma and allergy , which are responsible for increased production of IgE against these specific , antigens or allergens.

The exact cellular and molecular mechanism involved in the pathogenesis of allergic diseases is not yet well defined ( although some evidence is known ) . Which needs the close collaboration and cooperation of different filed of medicine.

On the genetic front . research is mostly focusing on the HLA complex , which is the most polymorphic human genetic system of known function . Studies have already provided evidence that the allergic immune response is controlled at the level of class ll region . The HLA Class ll background of the host play a key role in defining an allergen , and recent studies have indicated that IgE responsiveness to purified major allergens is closely linked  to a TCR , a major micro satellite defined polymorphism.

In fact a gene controlling total serum IgE level , and bronchial hyperactivity , which can lead to asthma has been mapped at chromosome 5q31-33. There is also evidence that a gene involved in atopy and bronchial hyperactivity maps at chromosome 11q13,close to the b chain of the high affinity IgE receptor (Fce-Rib).

At the cellular and moiecular level , immune response is characterized by increased IgE synthesis by B cells and by cytokine profile of allergen specific T cells . IgE antibodies bind to high affinity (type 1) Fce receptors present on the surface of mast cells and basophiles . Allergen induced Fe Rl cross linking then trigger the release of vasoactive mediators , chemo tactic factors ,and cytokines , which are responsible for the allergic cascade.