ER22/23EK AND TTH111I POLYMORPHISMS IN THE GLUCOCORTICOID RECEPTOR GENE IN PATIENTS WITH BRONCHIAL ASTHMA WITH REGARD TO THE AGE OF ONSET.

The objective of the study was to evaluate the frequency of the ER22/23EK and Tth111I polymorphisms in the glucocorticoid receptor gene (GR) in patients with early-onset and late-onset asthma (BA) and to assess the risk of its phenotype's development. We examined 553 BA patients and 95 apparently healthy individuals. The patients were divided into 2 groups depending on the age of BA onset: Group I included 282 patients with late-onset asthma, and group II included 271 patients with early-onset asthma. The ER22/23EK (rs 6189/6190) and Tth111I (rs10052957) polymorphisms in the GR gene were determined using polymerase chain reaction-restriction fragment length polymorphism analysis. Statistical analysis of obtained results was performed using SPSS-17 program. The analysis of frequency of genotypes and alleles for the ER22/23EK polymorphism in the GR gene with regard to the age of BA onset demonstrated a significant difference between patients with early-onset and late-onset asthma (p = 0.035). A significant difference was revealed in the distribution of alleles and genotypes for the Tth111I polymorphism in the GR gene between patients with early-onset BA and late-onset BA (p = 0.006). No correlation was found between the ER22/23EK polymorphism in the GR gene and late-onset BA in all genetic models; also, there was a reduction in the risk of early-onset BA observed in the dominant and additive models. No association was demonstrated between the Tth111I polymorphism in the GR gene and late-onset asthma, while a statistically significant correlation was shown with the risk of early-onset asthma in the dominant and super-dominant models. We established a significant difference in the distribution of alleles and genotypes for the ER22/23EK and Tth111I polymorphisms in the GR gene with regard to onset age; also, we found no association between these polymorphic variants and the development of late-onset asthma, but revealed a protective role of the ER22/23EK polymorphism in the GR gene in the dominant and additive inheritance models and of Tth111I polymorphism in the GR gene - in the dominant and super-dominant models.