Association of polymorphisms in the human IL4 and IL5 genes with atopic bronchial asthma and severity of the disease

Two polymorphisms in the IL4 (G/C 3'-UTR) and IL5 (C-703T) genes were studied in a sample of families whose probands had atopic bronchial asthma (BA) (66 families, n = 183) and in a group of non-cognate individuals with the severe form of the disease (n = 34). The samples were collected from the Russian population in the city of Tomsk (Russia). Using the transmission/disequilibrium test (TDT), a significant association of allele C-703 IL5 with BA was established (TDT = 4.923, p = 0.007 +/- 0.0007). The analysis of 40 individuals with mild asthma and 49 patients with the severe form of the disease revealed a negative association of genotype GG IL4 (OR = 0.39, 95% CI = 0.15-0.99, p = 0.035), and also a trend towards a positive association of the GC IL4 genotype (OR = 2.52, 95% CI = 0.98-6.57, p = 0.052) with mild BA. There was a concordance of the clinical classification of BA severity with the 'genotype' (McNemar's chi(2) test with continuity correction constituted 0.03, d.f. = 1, p = 0.859). These results suggest that polymorphisms in the IL4 and IL5 genes contribute to the susceptibility to atopic BA and could determine the clinical course of the disease.     

Contractile properties of smooth muscles of bronchial tubes at formation of hyperreactance of airways

Contractile properties of smooth muscles of bronchial tubes of porpoises in formation of hyperreactance airways, were studied. Sensitization by ovalbumin results in formation of hyperresponsiveness of the airways as shown in increase in amplitude of contractile responses to histaminergic influences and oppression of adrenergic relaxations of segments. Respiratory epithelium oppresses contractile responses of airways in intact animals to histaminergic influences. Influence of epithelium on adrenergic responses depends on precontractile factor: they increase in prereduction by histamine. In formation of hyperresponse, the epithelium loses ability to modulate responses of smooth muscles of the airways. Incubation segments of smooth muscles of the airways in interleukin 5 increases contractile responses to histaminergic influences. Receptor of interleukin 5 (the soluble fraction) neutralizes the effect of exogenous interleukin 5, and incubation of receptor of sensitized animals oppresses histaminergic contractile responses.     

Opisthorchis felineus and Metorchis bilis are the main agents of liver fluke infection of humans in Russia

Liver fluke infections are gradually transforming from a local problem of individual geographic regions to a widespread problem. The observed expansion is likely to be connected with the ever-increasing intensity of traffic flow and migration of the infected carriers between cities, regions, and countries. Opisthorchis felineus, the trematode belonging to the family Opisthorchiidae, is a well known causative agent of the infection called opisthorchiasis. Metorchis bilis, also a member of the family Opisthorchiidae, causes metorchiasis, a disease very close to opisthorchiasis in symptomatology. Genetic markers can be used to develop methods for differential diagnostics of these diseases. However, the questions connected with epidemiology of these trematode infections, their clinical characteristics, prognosis and therapy remain open. This review briefs the general biological characteristics of O. felineus and M. bilis persisting in various countries of Eurasia, their geographical range, epidemiology and molecular diagnostics of these liver flukes.     

Effect of additional disease (Comorbidity) on association of allergic rhinitis with KCNE4 gene rs12621643 variant

Analysis of association of allergic rhinitis with the KCNE4 gene rs12621643 variant was conducted in Russian residents of West Siberia (taking into account comorbidity with bronchial asthma). It was found that, among individuals without bronchial asthma, the frequencies of the KCNE4*G allele and KCNE4*G/G genotype are significantly higher in patients with rhinitis compared to individuals without it. At the same time, no association of rs12621643 with rhinitis was detected in the group of individuals with bronchial asthma. The data obtained indicate the association of the KCNE4 gene variability with allergic rhinitis, although the effect of this gene relative to the development of the disease can be leveled against a background of the manifestation of another atopic disease.     

Influence of nanosize particles of cobalt ferrite on contractile responses of smooth muscle segment of airways

Contractile responses of airways segments of porpoises inhaling nanopowder CoFe2O4 were stidued by means of a mechanographic method. Inhalation of the nanosize particles of CoFe2O4 in vivo and in vitro testing the nanomaterial on isolated smooth muscles led to potentiation histaminergic, cholinergic contractile activity in airways of porpoises and to strengthening of adrenergic relaxing answers. Nanosize particles vary amplitude of hyperpotassium reductions in smooth muscle segments of airways similarly to the effect of depolymerizing drug colchicine.     

Polymorphism of the Interleukin- and Interleukin Receptor Genes: Population Distribution and Association with Atopic Asthma

Population distribution and pathogenetic significance for bronchial asthma (BA) of the eight polymorphic variants of six interleukin- (IL) and interleukin receptor genes, C-589T, G/C 3"-UTRIL4, C-703T IL5 T113M IL9 Q551R, 150V IL4RA, G-80A IL5RA, and G1972A IL5RB, was examined. In the population samples of Russians, Tajiks, Buryats, and Tuvinians racial and ethnic specificity of these polymorphisms was established. These specific features were manifested as population-specific genetic portraits in respect of polymorphic allele frequencies. Analysis of the BA patients and their relatives from Tomsk by use of transmission/disequilibrium test (TDT) revealed the presence of a statistically significant association between the C-703 IL5 allele and the disease (P= 0.005). This is the first evidence of an association between the IL5 gene polymorphism and BA.     

Genome-wide association study of allergic diseases in Russians of West Siberia

Genome-wide association studies are currently considered as one of the most powerful tools for establishing the genetic basis of complex diseases. A number of such studies have been carried out for allergic diseases; however, in the Russian population, this analysis has not been performed so far. For the first time, we performed a genome-wide association study of allergic diseases in Russian residents of West Siberia. Two new loci associated with childhood bronchial asthma (20q13.12, rs2425656, P = 1.99 × 10⁻⁷; 1q32.1, rs3817222, rs12734001, P = 2.18 × 10⁻⁷ and 2.79 × 10⁻⁷, respectively) as well as one locus associated with allergic rhinitis (2q36.1, rs1597167, P = 3.69 × 10⁻⁷) were identified. Genes located in these loci, YWHAB and PPP1R12B for asthma and KCNE4 for allergic rhinitis, are suggested as new candidate genes for these diseases. It was also found that BAT1 (6p21.33), MAGI2 (7q21.11), and ACPL2 (3q23) are probably common (syntropic) genes of allergic disease and atopic sensitization. It was shown that RIT2 (18q12.3) and FSTL4 (5q31.1) genes can be involved in the control of lung function. The results of the study contribute to the body of data on genetic factors of allergy and expand the list of genes underlying these diseases.     

Azithromycin levels in the chorion tissue within the first three months of the pregnancy term]

The levels of azithromycin in the chorion tissue within the first 3 months of the pregnancy term (42 to 56 days post coitus) were determined. Three days after the use of azithromycin (Sumamed) the antibiotic concentration in the villi tissue was 0.065 to 0.26 mcg/mg (the average of 0.129 mcg/mg). The azithromycin concentration above 0.125 mcg/mg was detected in 38.5% of the women. The results confirmed the fact of significant azithromycin accumulation in the chorion tissue. The percentage of the azithromycin transplacental transfer within the above mentioned pregnancy term varied from 2.3 to 9.3 (the average of 4.6).     

Polymorphism of the theta1 and mu1 glutathione s-transferase genes (GSTT1, GSTM1) in patients with atopic bronchial asthma from the West Siberian region

Polymorphism for the GSTT1 and GSTM1 null alleles was analyzed in 69 patients with atopic bronchial asthma (BA) and in 57 healthy individuals from Tomsk. The two samples did not differ in frequencies of genotypes 0/0 and + of either gene or in frequencies of genotype combinations. No association was observed for GST and BA severity. Thus, the GST null alleles proved to be unimportant for BA.     

Polymorphism of interleukins and interleukin receptor genes: population distribution and association with atopic bronchial asthma

Population distribution and pathogenetic significance for bronchial asthma (BA) of the eight polymorphic variants of six interleukin--(IL) and interleukin receptor genes, C-589T, G/C 3'-UTR IL4, C-703T IL5, T113M IL9, Q551R, 150V IL4RA, and G1972A IL5RB, was examined. In the population samples of Russians, Tajiks, Buryats, and Tuvinians racial and ethnic specificity of these polymorphisms was established. These specific features were manifested as population-specific "enetic portraits" in respect of polymorphic allele frequencies. Analysis of the BA patients and their relatives from Tomsk by use of transmission/disequilibrium test (TDT) revealed the presence of a statistically significant association between the C-703 IL5 allele and the disease (P = 0.005). This is the first evidence of an association between the IL5 gene polymorphism and BA.