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.

[ROLE OF SLC2A9 AND ABCG2 GENE POLYMORPHISMS IN ORIGIN OF HYPERURICEMIA AND GOUT].

The polymorphisms V253I, Q126X, Q141K of SLC2A9 and ABCG2 genes were characterized. GCA и GTC haplotypes of Q126X and Q141K variants can be predictors of gout. The relationship of these polymorphisms with hyperuricaemia according to gender, metabolic syndrome components, with the response to allopurinol was analyzed. It has been established that Q141K polymorphism can directly modulate BCRP-mediated allopurinol and oxypurinol efflux, the K allele is associated with a lower reduction in serum uric acid in response to allopurinol treatment.

Bcl1 polymorphism of glucocorticoid receptor gene in patients with bronchial asthma with obesity.

The objective of this investigation was to analyze possible association between BclI polymorphism of glucocorticoid receptor gene and obesity in patients with bronchial asthma (BA). The study involved 188 patients with bronchial asthma and 95 apparently healthy adult individuals. Generally accepted assessments and examinations for BA diagnosis, and anthropometric, molecular-genetic and statistic methods of investigation were used in the research. It was found out that the patients with BA demonstrated higher body mass index (BMI) and higher ratio of fat centralization much more often, than the control group. Genotypes distribution for BclI polymorphism in patients with BA showed a statistically significant difference between patients with different BMI unlike the control group. Comparison of genotype frequency for BclI polymorphism in glucocorticoid receptor gene in individuals with different ratio of fat centralization in the control group and in the patients with BA separately showed statistically significant differences in the distribution of gene allelic variations only among the patients with BA. It was demonstrated that G/G genotype in the patients with visceral obesity was associated with BA.

[ASSOCIATION OF CYCLIC CITRULLINATED PEPTIDE ANTIBODIES LEVEL WITH RHEUMATOID ARTHRITIS ACTIVITY BASED ON GLUCOCORTICOID RECEPTOR GENE BBL1 POLYMORPHISM].

The ambiguity of facts on connection between glucocorticoid receptor gene (GR) Bcl1 polymorphism in rheumatoid arthritis (RA) and its activity as well as lack of facts on its association with serological variants of the desease, makes ir reasonable to investigate its connections between cyclic citrullinated peptide antibodiss (ACCP) concentration and clinico-laboratorial parameters of RA (DAS 28 desease activity score, C-reactive protein concentration (CRP) and erythrocyte sedimentation rate (ESR) level based on GR gene Bcl1 polymorphism. Study involved 161 RA patients aged over 40 as well as 96 healthy individuals. Routine examination of RA diagnostics, anthropometric and molecular genetic methods were used in the research. Statistical analysis of the results was performed using SPSS-17 program. It has been proved that there is no significant difference in GR gene Bcl1 polymorphism distribution based on DAS 28 RA desease activity score, ACCP concentration and ESR level. However, we have found out that G/G genotype bearers have positive correlation relationship between ACCP titre and RA activity by laboratorial parameters (CRP, ESR),DAS 28 score and rheumatoid factor (RF) which has not been found in C/C and C/G genotype bearing patients. The above indicates the association of G/G genotype by GR gene Bcl1 polymorphism with clinico-laboratorial parameters of RA inflammatory activity. In course of the study we have identified the existance of correlation relationship between ACCP concentration and DAS 28 score of RA activity, CRP concentration and ESR level in individuals bearing G/G gene by GR gene Bcl11 polymorphism gene. The association between GR gene Bcl1 polymorphism and clinico-laboratorial parameters of RA inflammatory activity has not been found.

[DISTRIBUTION OF GENOTYPES OF C825T POLYMORPHISM ß3-SUBUNIT G-PROTEIN GENE IN PATIENTS WITH ARTERIAL HYPERTENSION ACCORDING THE DEGREE OF OBESITY].

Arterial hypertension (AH) and obesity - risk factors for cardiovascular diseases and their complications, leading to high morbidity and mortality. These nosologies notedly linked, because have common etiological factors, pathophysiological mechanisms and genetic determination. The aim this research was to analyze the distribution of genotypes of the C825T polymorphism of ß3-subunit G-protein gene (GNB3) according the degree of obesity and to assess the risk of obesity in patients with AH. Patients were divided into three groups according the degree of obesity. We used clinical, anthropometric, instrumental, molecular-genetic and statistical methods. The significance of differences of alleles and genotypes frequency was determined by test χ². For comparing the groups used nonparametric Mann-Whitney and Kruskal-Wallis tests. A value of p<0.05 was considered significant. Our research showed high frequency of T allele carriers and C/T genotype among patients with hypertension and obesity (χ² = 27,976, p <0.001). In our study we observed the absence of statistically significantly difference (p = 0.677) of distribution of genotypes and alleles in patients with AH according the degree of obesity. The risk of obesity in T allele carriers was in 2.2 times higher than in C allele carriers in patients with AH. In summary, our study showed association of C825T polymorphism of the GNB3 with obesity, but did not prove the association this with the degree of obesity i patients with AH.

[BCL1 POLYMORPHISM OF GLUCOCORTICOID RECEPTOR GENE AND RESPIRATORY DISEASES].

The article analyses the results of investigating the connection between BCL1-polymorphism of glucocorticoid receptor gene and respiratory diseases. Its role in increasing sensitivity to glucocorticoids is proved here. The authors investigated the association of Bcl1 polymorphism with predisposition to bronchial asthma, chronic obstructive pulmonary disease, with the nicotine addiction degree and with progressing disorders of pulmonary function in cystic fibrosis.

Bcl1 polymorphism of glucocorticoids receptor gene and bronchial asthma.

The aim of our study was to investigate frequencies of alleles and genotypes of Bcl1 GR gene polymorphism and their correlation with prevalence of BA. Study involved 188 patients with BA and 95 healthy individuals. Bcl1 (rs41423247) polymorphism in exon 2 was determined by means of polymerase chain reaction with subsequent RFLP analysis (restriction fragment length polymorphism) by Fleury I. et al. with modifications. Statistical analysis of the results was performed using SPSS-17 program. The results showed statistically significant differences in genotypes distribution of BclI polymorphism of GR gene in the control group and in patients with BA. The frequency of genotypes distribution of Bcl1 polymorphism of GR gene in controls: C/C, C/G, G/G - 0,421/ 0,453/0,126; in patients with bronchial asthma: 0.228/0.426/0.346, respectively (p=0.001). It was found out that G/G-homozygotes have a fivefold higher risk of BA than those homozygous for C/C regardless of gender. We demonstrated that BA risk in females, homozygous for the minor allele, is higher (p=0.016) and men with G/G genotype of Bcl1 GR gene polymorphism have the highest risk of BA. Thus, G/G genotype of Bcl1 polymorphism of the glucocorticoid receptor gene is associated with the development of asthma.

[Effect of food deprivation on the proteolytic system in patients with atopic bronchial asthma concurrent with gastroduodenitis]. / Vplyv kharchovoï depryvatsiï na stan systemy proteolizu u khvorykh na atopichnu bronkhial'nu astmu v poiednanni z gastroduodenitom.

The article contains data on the state of the proteolysis system in the systemic blood flow and locally in the duodenal mucosa in those patients with bronchial asthma concurrent with gastroduodenitis. Results of fasting dietetic management versus medicamentous treatments showed a complete normalization of the protease-antiprotease imbalance with food deprivation.