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Atopy (allergy) is a class of immune system disorders that remains mysterious in many ways. In allergies, the immune system overreacts to innocuous substances called allergens, sometimes so severely that the patient's quality of life is drastically impacted. Allergic reactions can even cause death.
A person's susceptibility to developing allergy is largely determined by genes. Allergies run in families, and a number of loci have been associated with allergic disease.
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Genes Contributing to Allergy
It is well known that genetic factors contribute to allergies. Up to 40% of people in Western nations have a predisposed tendency to exaggerated IgE reactions and are therefore susceptible to developing atopic disease (Janewya et al. 2001). (IgE is the type of antibody implicated in the allergic response.)
A number of different genes have been implicated as contributors to the development of allergic diseases. Many of these are HLA-class II alleles (Movahedi et al. 2008). HLA stands for Human Leukocyte Antigen, and HLA genes are found on chromosome 6. They are known to be involved with the immune system, so it is no surprise to discover that they have an involvement in an immune disorder like allergy.
Genes on chromosomes 5q and 11q have also been implicated in the IgE pathway and therefore in the development of allergies (Janewya et al. 2001). The genes on chromosome 5 consist of a tightly linked cluster of genes that produce several immune system signalling molecules called cytokines. The gene on chromosome 11 codes for an IgE receptor protein.
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Allergy Genes: Complex and Specific
The genetic factors contributing to allergy are not simple, however. A number of separate genetic factors interact in complex ways to contribute to the development of atopic diseases. Research has shown that multiple distinct genetic pathways are involved; in other words, allergy may be caused by different genes in different people, and the interactions among various genes are part of the development of allergy (Finkelman and Vercelli 2007).
Genetic factors likely affect the development of specific allergies. Certain genes seem to predispose individuals to become allergic to some allergens but not to others. For example, a certain allele of a gene involved in major histocompatibility complex (MHC) class II is associated with IgE response to ragweed pollen (Janewya 2001). A person with this allele is more likely to become allergic to ragweed than other people, but is not necessarily more likely to become responsive to other allergens.
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Remaining Questions About Allergy Cause
Only about 10% of people with any atopic disease, such as asthma, hay fever, or eczema, also have a food allergy, but virtually all people with food allergies have other atopic diseases (Dreskin 2006). And out of all the countless proteins in the environment, only a small proportion cause allergies (Dreskin 2006). These facts are a few of the questions still facing immunologists who research the genetics of allergic diseases.
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- Dreskin, S. C., 2006. "The genetics of food allergy." Current Allergy and Asthma Reports 6(1):58-64.
- Finkelman, F. D., and D. Vercelli, 2007. "Advances in asthma, allergy mechanisms, and genetics in 2006." Journal of Allergy and Clinical Immunology 120(3):544-550.
- Janewya, Charles; Travers, Paul; Walport, Mark; and Shlomchik, Mark, 2001. Immunobiology: Fifth Edition. New York and London: Garland Science.
- Movahedi, M.; M. Moin, M. Gharagozlou, A. Aghamohammadi, S. Dianat, B. Moradi, M. H. Nicknam, B. Nikbin, A. Amirzargar, 2008. "Association of HLA class II Alleles with Childhood Asthma and Total IgE Levels." Iranian Journal of Asthma, Allergy, and Immunology 7(4):215-20.