At atopic diseases decrease β-adrenergic reactance comes to light. It is shown by a smaller degree glikogenolis, lipolis, increases arterial pressure and educations cAMPH in leukocytes at addition of adrenaline. There is growing evidence, that asthma and atop are genetically linked, although the genetic control of both diseases may be present at several levels sensitization and specific IgE responses, mediator release, end organ responsiveness or phenotype expression. It is assumed, that asthma may be a result of primary defect of β-2AR function, that an impaired β-adrenergic function may be also related to IgE responsiveness and atopy.
New exciting data are related to the recently found polymorphism of the β-2AR. The gene for the β-2AR, which is localized close to the IL-4 gene duster on chromosome Sq, has been previously cloned, and sequenced. It is established that several point mutations exist within the gene coding region, resulting in changes in the amino acids sequence. It is shown, that the changes in the aminoacid sequence of the extracellular aminoterminus of the receptor affected the function of the receptor. For example, the presence of glycine at position 16 (Glyl6) was associated with enhanced regulation of the receptor in the response to agonist as compared to arginine at this position (Arg16), and substitution of Glu for Gln at position 27 resulted in a decreased regulation of the receptor. It is assumed, that this polymorphism may affect bronchial smooth muscle function in vivo. In fact, study of the Gln/Glu 27 polymorphism, and airway hyperreactivity in a group of patients with mild to moderate asthma revealed that Gln27 homozygotes had a four-fold higher bronchial hyperresponsive-ness to methacholine (lower threshold dose), than patients who were homozygous for the Glu27 form of the receptor; heterozygotes had an intermediate hyperreactivity. Population study, demonstrated similar frequency of Gly/Arg16 and Glu/Gln27 polymorphism in asthmatic and normal subjects. It is indicating, that polymorphism is not a major cause of asthma. However, comparison of the frequency of the β-2AR genetic variants in patients with nocturnal and non-nocturnal asthma reveled, that the Gly 16 allele was significantly more frequent in the nocturnal group as compared to the non-nocturnal group.
These data indicate, that β-2AR polymorphism may be closely related to the asthmatic phenotype, and severity of the disease. Since β-2AR are present on immune cells like lymphocytes, macrophages and granulocytes, being involved in modulation of inflammatory mediators and cytokines release, it has been postulated that, genetic polymorphism of β-2AR may also be associated with the expression of the atopic phenotype.
The article is admitted to the International Scientific Conference " Priorities of Science and Technology Development: Educational Technologies "; Greece (Athens - Argolida - Delphi - Meteora - Athens), 2007, March 23-30; came to the editorial office on 13.03.07