Text V. Genetic Aspects of Atopic Disorders

Although hereditary components in the development of allergic manifestations have generally been recognized, the exact character of inheritance of allergies has so far eluded researchers. The understanding of the exact genetic mechanisms involved in the development of allergic reaction would shed light on the underlying biochemical reactions and, thus, contribute to treatment and prevention. In addition, it would lead to more precise predictions about recurrence risks.

Although the earlier studies have been useful for counseling families about risks of developing allergy, breakthroughs in understanding the etiology of allergic disease did not come until the 1970s.

March et al. set out to define limits of IgE levels for the genotype associated with atopic disease, identifying those IgE levels that would cause the least overlap between atopic and nonatopic individuals. Complex analysis supported the hypothesis of a major locus as well as significant influence for IgE regulation. This locus would have two genes: a dominant gene suppressing high levels of IgE and recessive gene, which in the homozygous state would lead to high serum IgE levels.

There are two most common HLA gene combinations in Europeans. These patterns occur with frequency of 5% and 3%, respectively, which is 20-30 times more frequent than would be expected. It appears that individuals carrying these patterns have some selective advantage. For instance, the gene or genes could have increased the resistance of the individual to some virus or other organisms causing disease and death in those not carrying the gene.

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