BACKGROUND: Bronchial asthma is a chronic respiratory disorder characterized by airway inflammation, airway hyperresponsiveness, and periodic reversible airway obstruction. Subtype 2 helperT cell (T(H)2) cytokines play an important role in the development of allergic airway inflammation in patients with bronchial asthma. OBJECTIVE: To investigate whether the single-nucleotide polymorphisms (SNPs) Ile75Val and Gln576Arg in the IL4RA gene, -33C>T in the IL4 gene, and Gly237Glu in the FCER1B gene contribute to the development and severity of atopic bronchial asthma in Russian patients from Moscow. METHODS: We analyzed DNA samples from 224 patients with atopic bronchial asthma and 172 healthy individuals. Genotyping was performed by primer extension followed by matrix-assisted laser desorption/ionization-time of flight mass spectrometry. RESULTS: We observed a moderate association between the Arg/Arg genotype of Gln576Arg and protection against asthma (odds ratio [OR], 0.16; P < .012) and a strong association between the T allele and TT genotype of -33C> and atopic bronchial asthma (OR, 1.91 and 4.65, respectively; P < .0001). Carriers of the C allele had a reduced risk of asthma (OR, 0.53; P < .0001). Furthermore, we found that the TT genotype of -33C>T correlated with higher concentrations of total serum immunoglobulin E and interleukin 4 than the CC and CT genotypes. CONCLUSION: We found an association between atopic bronchial asthma and the SNPs Gln576Arg in IL4RA and -33C>T in IL4. IL4RA and IL4 seem to be involved in the pathogenesis of asthma.
Asthma/genetics , Interleukin-4/genetics , Receptors, IgE/genetics , Th2 Cells/physiology , Adult , Airway Obstruction/genetics , Airway Obstruction/immunology , Airway Obstruction/metabolism , Alleles , Asthma/immunology , Asthma/metabolism , Case-Control Studies , Female , Genetic Predisposition to Disease , Genotype , Humans , Immunoglobulin E/genetics , Inflammation/genetics , Inflammation/metabolism , Interleukin-4/metabolism , Male , Moscow , Odds Ratio , Polymorphism, Single Nucleotide , Th2 Cells/immunology , Th2 Cells/metabolism , White People/genetics
To test the M31R and R335C polymorphisms of the Il8RA gene for association with atopic bronchial asthma (BA), the allele and genotype frequency distributions of the polymorphisms were studied in Russian patients from Moscow and Buryat patients from Ulan-Ude. The study involved two Russian groups, one including 291 DNA samples of patients with atopic BA, and the other, 266 DNA samples of healthy people. The two Buryat groups included 124 and 152 DNA samples from patients with atopic BA and healthy people, respectively. The M31R polymorphism proved to be associated with atopic BA in Russians. Allele Arg and genotype Met/Arg suggested a higher risk of BA (OR= 4.45, P = 0.003 and OR = 4.58, P = 0.003, respectively), while allele Met and genotype Met/Metwere associated with a lower risk (OR = 0.22, P = 0.003 and OR = 0.22, P = 0.003, respectively). The R335C polymorphism was not associated with atopic BA in Russians and was in Buryats. Allele Arg and homozygous genotype Arg/Arg suggested a higher risk of the disease (OR = 3.06, P = 0.030 and OR = 3.20, P = 0.027, respectively), while allele Cys and genotype Arg/Cys suggested a lower risk (OR = 0.33, P = 0.030 and OR = 0.31, P = 0.027, respectively). The results support the role of the IL8RA gene in atopic BA.
Asthma , Genetic Predisposition to Disease , Homozygote , Polymorphism, Genetic , Receptors, Interleukin-8A/genetics , Asthma/ethnology , Asthma/genetics , Female , Genetic Predisposition to Disease/ethnology , Genetic Predisposition to Disease/genetics , Humans , Male , Risk Factors , Siberia/ethnology
In order to investigate whether single nucleotide polymorphisms G(+2722)C and 3020insC in CARD15 gene and Asp299Gly in TLR4 gene contribute to atopic bronchial asthma we performed a comparative analysis of alleles and genotypes frequencies of these polymorphisms in Russian patients from Moscow. DNA samples from 283 patients with atopic bronchial asthma and 227 healthy donors were genotyped. There were associations neither of G(+2722)C and 3020insC in CARD15 gene and Asp299Gly in TLR4 gene with asthma nor of markers of CARD15 gene with asthma severity. Haplotype frequency analysis of CARD15 gene polymorphisms did not reveal significant difference between groups. However, a strong association was found between Asp299Gly and asthma severity. Allele Asp of this marker showed association with mild atopic bronchial asthma and allele Gl--with moderate/severe asthma = 0.47, 95% CI [0.24-0.93] i OR = 2.12, 95% CI [1.08-4.18] respectively).
Asthma/genetics , Nod2 Signaling Adaptor Protein/genetics , Polymorphism, Single Nucleotide , Toll-Like Receptor 4/genetics , Adult , Alleles , Case-Control Studies , Female , Gene Frequency , Genetic Predisposition to Disease , Genotype , Haplotypes , Humans , Male , Middle Aged , Moscow , Polymerase Chain Reaction , Severity of Illness Index , Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
A comparative analysis of allele and genotype distribution of C(-1055)T and R130Q IL13 gene polymorphisms has been performed in Russian patients from the Moscow region. In the study, 283 DNA specimens of atopic bronchial asthma (BA) patients and 227 DNA specimens of healthy donors were used. No association of these markers with ABA development as well as with total IgE concentration has been found. Haplotype frequency analysis did not reveal significant difference between samples. However, significant association ofC(-1055)Tpolymorphism with the disease severity has been revealed (OR = 2.39, 95% confidence interval 1.44-3.98, p = 0.001). Therefore, C(-1055)T polymorphism was shown to be associated with atopic BA progression.
Asthma/immunology , Interleukin-13/genetics , Adult , Asthma/blood , Asthma/genetics , Disease Progression , Female , Genetic Markers , Humans , Immunoglobulin A/blood , Male , Moscow , Polymorphism, Genetic , Young Adult
