A complete screening of the IL4 gene

Background: Susceptibility to the development of bronchial asthma (BA) and other atopic diseases is known to be associated with genetic components. Objective: To evaluate the possible role of the polymorphisms in IL-4 gene promoters (C-33T, C-590T and G-1098T) in modulating allergic response and asthma in the Russian population. Methods: The polymorphism analysis was carried out by PCR-RFLP; IL-4 and total IgE concentrations were determined by ELISA. Results: In the case group, the T allele was found at frequencies of 74% (C-33T), 51% (C-590T) and 5% (G-1098T); in the control group the frequencies were 22, 42 and 8%, respectively. Only the C-33T polymorphism was associated with BA. The concentrations of total IgE and serum IL-4 were raised in the case group, while in the control group they were normal. Serum IL-4 level depended on C-33T polymorphism both in the case and control groups, the mutant T allele promoting its increase. The dependence on C-590T polymorphism was detected only in the case group. As for the total IgE level, in both cases it depended on the polymorphism in the case group rather than the control. G-1098T polymorphism did not demonstrate any correlations with total IgE or serum IL-4 levels. All 3 polymorphisms did not affect the severity of BA in the case group. On the basis of the computer analysis, we propose that the T-33C region is the CREB-binding site. Conclusions: Our data suggest that IL-4 promoter polymorphism in the Russian population might play a role both conferring susceptibility to BA and modulating the levels of serum IL-4 and total IgE.

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Allelic Polymorphisms in the Interleukin-4 Promoter Regions and Their Association with Bronchial Asthma among the Russian Population

Gervaziev

Kaznacheev

Gervazieva

2006

“…The population used in this study has been described in detail previously [14, 15, 16]. Therefore, only methods pertaining to this analysis are given below.…”

Section: Methodsmentioning

confidence: 99%

“…No significant differences between the study populations from both cities were found with respect to population characteristics [15]. The schools sent parental self-completion questionnaires on to the families.…”

Section: Methodsmentioning

confidence: 99%

A Comprehensive Analysis of Interleukin-4 Receptor Polymorphisms and Their Association with Atopy and IgE Regulation in Childhood

Woitsch

Carr

Stachel

et al. 2004

Self Cite

Background: The interleukin (IL) 4/IL13 pathway is involved in the regulation of IgE production associated with atopic diseases. Numerous polymorphisms have been identified in the coding region of the IL4 receptor α chain (IL4Ra) and previous association studies have shown conflicting results. Based on their putative functional role, polymorphisms A148G, T1432C and A1652G, located in the coding region of IL4Ra, were selected for association and haplotype studies in a large German population sample (n = 1,120). Methods: Genotyping was performed using allele-specific PCR and restriction-enzyme-based assays. Haplotypes were estimated, and population-derived IgE percentiles (50% IgE >60 IU/ml, 66% IgE >115 IU/ml and 90% IgE >457 IU/ml) were calculated as outcome variables in a haplotype trend regression analysis. Results: In our population, only polymorphism T1432C showed a trend for a protective effect against atopic rhinitis (odds ratio, OR: 0.52, 95% confidence interval, CI: 0.26–1.02, p = 0.05). When haplotypes were calculated, one haplotype was significantly associated with elevated serum IgE levels at the 50th percentile (OR 1.60, 95% CI 1.08–2.37, p = 0.02). Conclusions: These data indicate that IL4Ra polymorphisms, although suggested to be functionally relevant by in vitro studies, have only a minor influence on IgE regulation in our large population sample.

“…A variant of the IL4 gene promoter, –590 C/T, has been shown to associate in vitro with IL-4 activity and show higher binding activity to nuclear transcription factors and alteration in an electrophoretic mobility shift assay, allele T being the high producer [19]. In vivo allele T has been associated with high total IgE levels, asthma, and atopy in several studies [20,21,22,23,24,25,26,27,28]. …”

Section: Introductionmentioning

confidence: 99%

Epistatic Effect of TLR4 and IL4 Genes on the Risk of Asthma in Females

Ådjers

Karjalainen²,

Pessi

et al. 2005

Background: Many studies have demonstrated a connection between asthma and T-cell cytokine genes, such as genes coding for interleukin-4 (IL4) and IL-13, which are involved in the regulation of the TH1/TH2 balance. The toll-like receptor 4 (TLR4), the principal receptor for bacterial endotoxin, has attracted attention as a potential risk factor for asthma. We examined whether the polymorphisms of the TLR4 (A/G at +896) and IL4 (C/T at –590) showed an epistatic effect on the risk of asthma or atopy. Methods: Gene polymorphism analyses and skin prick tests were performed on asthmatic and nonasthmatic adult subjects of a Finnish population-based case-control study. The phenotype studied was persistent asthma. Results: The results showed that genotypes of neither the TLR4 SNP at +896 nor IL4 SNP at –590 were separately found to be associated with asthma. However, the female carriers of allele G (i.e. genotype AG or GG) of TLR4 and allele T (genotype CT or TT) of IL4 had a significantly increased risk for asthma. No association of these genes and atopy was found. Conclusions: Our results indicate that in females the TLR4 and IL4 genes show an epistatic effect on the risk of asthma. The low LPS-responsive allele G of TLR4 and high IgE production allele T of IL4 were found to be the predisposing combination. However, there was no epistatic effect on the risk of atopy.