IL-4 C33T Research Articles

IL-4 and its polymorphism (<i>IL4</i>-589C/T) in cervical neoplasia

The transition of cervical neoplasia (CIN) to cervical cancer occurs with the active participation of IL-4, for which both pro- and antitumor effects have been shown with tumors of various localizations. The expression of cytokines is regulated at the transcriptional level in the promoter region of the gene. It has been shown that the genotype IL4 (589C/T) (rs2243250) is associated with the development of gastric and breast cancer. The contribution of IL-4 genotypic variations to the development of CIN has not yet been studied. The aim of the study was to assess the risk of developing cervical neoplasia by the presence polymorphism of IL4 (589C/T) and the level of IL-4. The object of the study was circulating neutrophils, serum and genomic DNA of 36 patients with CIN and 20 women without dysplasia (comparison group). Using ELISA, the level of IL-4 was determined in neutrophil lysate and serum. Phagocytic activity and adhesive ability (CD11b) of neutrophils were assessed. Allele-specific real-time PCR using Taq-Man probes was used to analyze of the IL4 589C/T (rs2243250). Statistical processing was carried out using Statistica 13 and Jamovi 1.6.5.0. As a result of the study, it was found that the level of IL-4 in serum and circulating neutrophils in patients with CIN is significantly higher than in the comparison group. The -589C* allele of the IL4 gene and the TT genotype are more common in the group with CIN (55.5%) than in the control (25%). At the same time, a direct relationship was established between the presence of polymorphism and increased adhesive ability and with indicators of the phagocytic number of circulating neutrophils. Analysis of the incidence of IL4 C589T by the «case-control» method showed that the chances of CIN formation in carriers of the -589C allele and the TT genotype were 3.75 (95% CI: 1.013 - 13.880, Chi-square = 4.161, p = 0.042). The -589C* allele and TT IL4 genotype, neutrophil and serum IL-4 levels are associated with HPV infection. Using a binary logistic regression model, we demonstrated the possibility of using IL-4 levels in circulating neutrophils and IL-4 gene polymorphism (589C/T) for the differential diagnosis of patients with CIN (χ2 = 15.6, p = 0.001). Significant significance for their combination was assessed by ROC-curve analysis (IL-4 in neutrophils; IL4 (-589С*), 75% probability. Thus, the IL4 (589C/T) is associated with the adhesive and phagocytic activity of circulating neutrophils. In HPV-infected patients, IL4 gene polymorphism (589C/T) can serve as a marker for early detection and prognosis of CIN.

Interleukin-4 gene polymorphism (C33T) and the risk of the asthma: a meta-analysis based on 24 publications

BackgroundPrevious studies evaluated the association of IL-4 C33T polymorphism and risk of bronchial asthma but failed to establish a consistent conclusive association. In the present meta-analysis, we intend to define a more reliable estimate of the association in the presence of filling published literature.MethodsAn exhaustive search in Web of Science, Scopus, and PubMed databases was performed to identify all relevant publications before September 2020, and 24 publications (28 studies) with 6587 cases and 8408 controls were included in final analysis. The association between polymorphism and risk of asthma were measured by Odd ratios (ORs) and 95% confidence intervals (CIs). Moreover, Cochran’s Q and the I2 statistics were used to evaluate the degree of heterogeneity between studies.ResultsIn the overall study populations, a significant positive association was detected under all genotype models and announced the IL-4 C33T polymorphism as a potential risk factor in the pathogenesis of asthma. In the subgroup analysis by age, a significant association between IL-4 C33T polymorphism and risk of asthma in different age groups was identified in allelic model, which highlighted the predisposing role of the T allele for the asthma risk in all three age groups. Furthermore, the results of subgroup analysis by continent were heterogenous. Accordingly, IL-4 C33T polymorphism was a risk factor in Europeans (all models except heterozygote comparison), Americans (all models except recessive and homozygote comparison) and Asians (just recessive and allelic model). Finally, the ethnicity-specific analysis disclosed a significant association between IL-4 C33T polymorphism and asthma risk in Caucasians (all genotype models except heterozygote comparison), while this association was not significant in African-Americans.ConclusionsThis study suggests that IL-4 C33T polymorphism potentially acts as a risk factor for asthma in different ethnicities and age groups.

Effect of cytokine genes and season of birth on personality

To evaluate the interaction effects of season of birth and immune system genes on the personality traits 'Novelty seeking' (NS) and 'Self-directedness' (SD). Based on results on an influence of the immune system on the brain processes, the authors hypothesized that the interaction of immune system genes and season of birth, which is relevant for immune phenotype, can contribute to the development of personality traits. NS and SD were measured in 336 healthy volunteers, aged from 16 to 67 years, using the Temperament and Character Inventory (TCI-125). IL1B C3954T, IL4 C-589T, IL13 C1112T and TNFA G-308A polymorphisms were genotyped. An interaction effect of IL4 C-589T and season of birth on the personality traits was found (F2,322=6.03, pcorr=0.011, η2=0.04). Carriers of the minor allele T, who were born in winter, had lower NS and higher SD. There was a nominal main effect of genotype on SD (F=5.44, p=0.020) as well, with higher SD scores in carriers of the allele T compared to the CC genotype. The results suggest that the etiology of personality and immune characteristics can share common genetic elements including IL-4.

Role of Interleukin-4, Interleukin-10, and Tumor Necrosis Factor-α Polymorphic Genes in the Pathogenesis of Occupational Allergic Dermatoses.

Study of polymorphic genes of pro- and anti-inflammatory cytokines (IL-4, IL-10, TNF-α) in patients with occupational allergic dermatoses showed significantly higher frequency of polymorphic variants of cytokine genes IL4 C589T, IL10 C819T, IL10 G1082A, IL10 C592A, and TNF G308A in comparison with the population control. The presence of homozygous variant IL10 G1082A--AA in 80% cases characterizes early disease development, i.e. within 3 years after the first exposure to the occupational factor.

Identification of IL13 C1923T as a Single Nucleotide Polymorphism for Asthma in Children from Mauritius.

Background: Research increasingly suggests that asthma is a familial and hereditary disorder and that genetic and environmental factors play a key role in its pathogenesis. Objective: The aim of this study was to investigate the associations between 10 single nucleotide polymorphism (SNP) loci in the development of asthma in children from the Mauritian population. Methods: The study population consisted of 193 children with asthma and 189 healthy controls from the Mauritian population. Asthma was diagnosed in accordance with the American Thoracic Society criteria. TaqMan real-time quantitative polymerase chain reaction was used to detect the genotypes of the SNP loci. Results: No statistically significant differences (p>0.05) were found between the experimental and control group in genotype distribution among nine of the loci (MS4A2 E237G, MS4A2 C-109T, ADRB2 R16G, IL4RA Q551R, IL4RA I75V, IL4 C-590T, IL13 A2044G, IL13 C-1112T, and CHI3L1 C-131G). However, the frequency of IL13 C1923T TT in the asthma group was significantly higher than in the control group (odds ratio=2.119, p=0.033) suggesting that carriers of IL13 C1923T TT in the Mauritian population may have a more significant risk of developing asthma. Conclusion: The nine loci have little contribution to the development of childhood asthma in the Mauritian population. IL13 C1923T TT has been detected to be the susceptible genotype and may have a significant effect on the pathogenesis of childhood asthma in the Mauritian population.

Lack of Association between the IL-13 C-1112T, G2044A Polymorphisms and Graves’ Disease Risk: Evidence from a Meta-analysis

Background: Previous studies have provided conflicting evidence implicating the IL-13 C-1112T and G2044A polymorphisms in Graves’ disease (GD) risk. We undertook a meta-analysis to address this issue.Methods: The Medline, Pubmed and Web of Science databases were searched for published case-control studies investigating the relation of the IL-13 C-1112T and G2044A polymorphisms with GD risk. Data were extracted using standardized forms and odds ratios (OR) with 95% confidence intervals (CI) were calculated.Results: Available data did not suggest an association between any of the two IL-13 polymorphisms and GD risk. For the C-1112T polymorphism, the combined OR was 0.96 (95% CI: 0.77–1.19) for dominant model (TT + CT vs CC), 0.97 (95% CI: 0.69–1.38) for recessive model (TT vs CT + CC), and 0.97 (95% CI: 0.68–1.39) for homozygote model (TT vs CC). ORs for the G2044A polymorphism were similar. In subgroup analyses stratified by ethnicity, we also did not find associations between these two variants and GD risk in Asians or Caucasians. Sensitivity analyses by excluding each of the involved study in turn did not change the pooled results.Conclusion: The IL-13 C-1112T and G2044A polymorphisms are not associated with GD risk.

The correlation between IL13 C-1112T polymorphism and cancer risk:a meta-analysis

Objective To study the correlation between IL13 C-1112T polymorphism and cancer risk.Methods PubMed database was utilized to search articles related to correlation between ILl3 C-1112T polymorphism and cancer risk.All the statistical analysis was performed by STATA software.Results No association was observed in the overall analysis.However,in the stratified analysis,we found IL13 C-1112T polymorphism was significantly associated with decreased risk of glioma(TC vs.CC:OR=0.72,95％CI=0.55-0.93;TC + TT vs.CC:OR=0.76,95％CI=0.62-0.89).Conclusion IL13 C-1112T polymorphism may be correlated with glioma risk. Key words: IL-13; Polymorphism; Meta-analysis; Cancer risk

Association Between the Interleukin-4 Gene C-589T and C+33T Polymorphisms and Asthma Risk: A Meta-analysis

A large number of studies have investigated the correlation between the interleukin (IL)-4 C-589T and C+33T polymorphisms and asthma susceptibility. However, the results are inconsistent. The objective of this study is to explore the association between the IL-4 C-589T and C+33T polymorphisms and asthma risk using meta-analysis. A total of 35 studies (31 concerning C-589T polymorphism and asthma risk with 4737 asthmatics and 6389 controls and 14 studies regarding C+33T polymorphism and asthma risk with 2544 asthmatics and 4049 controls) were included in this meta-analysis. The IL-4 C-589T polymorphism was associated with increased asthma risk in a dominant genetic model (odds ratio [OR] [95% confidence interval (CI)] = 1.284 [1.131-1.459] for TT + TC vs. CC). In the subgroup analyses by ethnicity, age and atopic status of asthmatics, significantly increased risks of asthma were found both in Asians (OR [95% CI] = 1.301 [1.003-1.689]) and Caucasians (OR [95% CI] = 1.314 [1.061-1.628]) and in both adults (OR [95% CI] = 1.299 [1.098-1.537]) and children (OR [95% CI] = 1.464 [1.044-2.052]). As for the C+33T polymorphism, the results showed that it was correlated with elevated asthma risk in a recessive genetic model (OR [95% CI] = 1.744 [1.215-2.504] for TT vs. CT + CC). After stratifying analyses by ethnicity, age and atopic status of asthmatics, significantly increased asthma risks were observed in Asians (OR [95% CI] = 1.223 [1.037-1.442]), Caucasians (OR [95% CI] = 3.036 [1.224-7.529]), and children (OR [95% CI] = 1.300 [1.075-1.573]) in a recessive genetic model. This meta-analysis suggests that the IL-4 C-589T and C+33T polymorphisms may be risk factors for asthma.

Association of interleukin‐13 C‐1112T and G+2044A polymorphisms with asthma: A meta‐analysis

Polymorphisms in the IL13 gene have been reported to be associated with susceptibility to asthma. However, a number of studies have shown inconsistent results. A meta-analysis was performed to investigate whether polymorphisms in the IL13 gene were associated with the risk of asthma. Searches were performed of the Medline and Chinese National Knowledge Infrastructure (CNKI) databases, covering all papers published up to 31 August 2010. A recently proposed logistic regression-based method for meta-analysis of case-control genetic association studies was used to analyse pooled data. All statistical analyses were performed using stata version 10.0 software. The IL13 C-1112T and G+2044A polymorphisms were investigated in 10 and 14 studies, respectively. The summary estimates suggested that both these polymorphisms were associated with susceptibility to asthma. Carriers of the IL13 -1112T allele had a 38.9% increased risk of asthma compared with homozygotes (-1112CC) (odds ratio (OR) 1.389, 95% confidence interval (CI): 1.103-1.749). Carriers of the IL13+2044A allele had a 40.0% increased risk of asthma compared with homozygotes (+2044GG) (OR 1.400, 95% CI: 1.137-1.724). In a subgroup analysis by ethnicity, the IL13 -1112T allele was associated with an increased risk of asthma among Caucasians (OR 1.629, 95% CI: 1.255-2.113) but not among Asians, and the IL13+2044A allele was associated with an increased risk of asthma among Asians (OR 1.436, 95% CI: 1.101-1.873) but not among Caucasians. This meta-analysis indicated that the IL13 C-1112T and G+2044A polymorphisms predispose to asthma. Further studies, including pooling of individual data to facilitate evaluation of gene-gene and gene-environment interactions between these IL13 gene polymorphisms and asthma susceptibility, are recommended.

Helicobacter pylori infection and cytokine gene polymorphisms in Uzbeks.

Recent studies have reported that Helicobacter pylori (H. pylori) persistent infection and gastric atrophy development were associated with genetic polymorphisms of cytokines. This study aimed to determine possible associations of host genotypes with the seropositivity of anti-H. pylori IgG and anti-CagA IgG, as well as gastric atrophy measured with serum pepsinogens (PG) among an Uzbek population. Subjects were 84 patients with peptic ulcer disease, 35 with other miscellaneous diseases, and 48 healthy persons, for a total of 167 participants. Using a polymerase chain reaction with confronting two-pair primers, their DNA was genotyped for polymorphisms of interleukins (IL) (IL-1B C-31T, IL-2 T-330G, IL-4 C-33T, IL-8 T-251A, IL-10 T-819C, and IL-13 C-1111T) and tumor necrosis factor A (TNF-A) (C-857T and T-1031C). Among 167 participants, 124 (74.9%) were anti-H. pylori IgG seropositive, 142 (85.6%) were anti-CagA IgG seropositive, and 44 (26.3%) exhibited gastric atrophy (PG1 < 70 ng/ml and PG1/PG2<3). The adjusted odds ratio (OR) of IL-4 -33CT for anti-H. pylori IgG seropositivity was significant; OR = 2.33 (95% confidence interval (CI), 1.04-5.19), relative to -33CC. In addition, those with TNF-A-1031TC had a significantly increased risk for anti-H. pylori IgG seropositivity; OR = 2.82 (95% CI, 1.05-7.57), relative to -1031TT. No alleles were associated with the risk of anti-CagA IgG seropositivity or gastric atrophy. The significant associations with cytokine polymorphisms indicated that genetic traits might play a role in the persistent infection of H. pylori among Uzbeks. In addition to confirming the above associations, lifestyle interactions with the genotypes also remain to be elucidated.

Gender-specific effects of cytokine gene polymorphisms on childhood vaccine responses

Cytokine gene polymorphisms affect vaccine responses and gender-specific effects are known for many phenotypes. Therefore, this study investigated gender-specific effects of cytokine gene polymorphisms on vaccine responses. In 263 2-year-old subjects selected for parental history of atopy, boys with IL-4 C-589T and IL-4Rα I50V genotypes associated with atopy had increased Diptheria Toxoid (DiphTox) and Tetanus Toxoid (TetTox) responses compared with the remaining alleles (IL-4 C-589T: DipTox p = 0.01, TetTox p = 0.04; IL-4Rα.I50V: DipTox p = 0.04, TetTox p = 0.08). Contrastingly, girls with IL-10 -592C genotypes associated with atopy had lower levels of DiphTox ( p = 0.03) and TetTox ( p = 0.02) responses compared with the remaining allele. Additionally, interaction effects were found for IL-4 C-589T ( p = 0.01) and IL-4Rα I50V ( p = 0.04) polymorphisms. In conclusion, these findings support the interaction of primary genetic and modifying factors on vaccine responses and the importance of atopic genetics to these responses.

Allergy-Related Polymorphisms Influence Glioma Status and Serum IgE Levels

Previous studies have shown that glioma patients report allergies less frequently than controls, harbor lower atopy-associated IgE levels, and harbor different frequencies of polymorphisms in the IL13 and IL4 pathways than controls. We sought to confirm this latter result and extend the analysis to IgE levels. Glioma patients (n = 456) and controls (n = 541) were genotyped for genetic variants in IL4, IL4R, and IL13 and tested for total IgE levels (n = 248 controls and 289 cases). Among Whites, IL4 and IL4R polymorphisms and haplotypes were neither significantly associated with IgE levels in controls nor associated with glioma status. IL13 R110G and C-1112T were associated with increased IgE levels in controls (P < 0.001 and P = 0.04, respectively), and IL13 C-1112T was inversely associated with case-control status (P = 0.05, test for trend in dose model). An IL4R haplotype was borderline associated with increased risk in case-control analysis [odds ratio (OR), 1.5; 95% confidence interval (95% CI), 1.0-2.3]. In addition, a rare haplotype for IL4 was associated with decreased risk (OR, 0.23; 95% CI, 0.07-0.83), and a common haplotype in IL13 was associated with decreased risk (OR, 0.73; 95% CI, 0.53-1.00). Our data provide evidence for a role of IL13 polymorphisms on IgE levels and a role for IL4, IL4R, and IL13 haplotypes on case-control status. We did not find any evidence that the interleukin (IL) polymorphisms exerted their effect on glioma risk via their effects on IgE levels. Further exploration of immune susceptibility factors, including genetics, in glioma etiology is advisable.

Impact of serum levels and gene polymorphism of cytokines on chronic hepatitis C infection

The factors leading to clearance or persistent infection of hepatitis C virus (HCV) were not well defined, and the importance of the host immune response has been highlighted. Therefore, the impact of the serum concentration and genetic polymorphism of several cytokines on the outcome of HCV infection warrant additional study. Enzyme-linked immunosorbent assay was employed to measure serum tumor necrosis factor-alpha (TNF-alpha), interleukin (IL)-4, and IL-10 concentrations on 72 hepatitis C patients and 180 controls. Furthermore, the association between single nucleotide polymorphism (SNP) of genes of these cytokines and hepatitis C infection was evaluated by polymerase chain reaction- restriction fragment length polymorphism and statistical analysis. These analyzed SNPs of cytokines included TNF-alpha G238A, TNF-alpha G308A, IL-4 C589T, IL-10 A1082G, IL-10 T819C, and IL-10 A592C. Serum levels of TNF-mu alpha, IL-4, and IL-10 were significantly higher in hepatitis C patients than that of controls (P < 0.001). Furthermore, the distribution of TNF-alpha G308A genotypes and alleles, but not others, was statistically different between patients and controls (P < 0.05). These data suggested the distribution of polymorphism at TNF-alpha G308A may be different between normal subjects and patients with chronic infection of hepatitis C.

Polymorphismen in der IL-4/IL-13-Signalkaskade beeinflussen die IgE-Regulation und Asthma bronchiale

Background: The IL-4/IL-13 pathway plays a critical role in the IgE regulation and the development of asthma. Previous studies have described an association between genetic alterations in single genes of the IL-4/IL-13 pathway and these two phenotypes. In this study, we analyzed the combined effect of different genetic alterations in the genes of the IL-4/IL-13 pathway (IL-4, IL-13, IL-4Ra and STAT6) on the regulation of IgE and the development of asthma. Methods: In a large cross-sectional study population (ISAAC II) of 1,120 children, aged 9-11 years, 18 polymorphisms in the respective genes of the IL-4/IL-13 pathway were genotyped. Based on linkage disequilibrium and functional relevance, one polymorphism of each gene (IL-4 C-589T, IL-13 C-1112T, IL-4Ra A148G und STAT6 C2892T) was selected to assess gene by gene interactions using a stepwise haplotype procedure following a Cordell model. Results: Certain combinations of polymorphisms in the IL-4/IL-13 pathway significantly influence IgE regulation. Furthermore, a significant protective effect towards the development of asthma was identified. Compared to single gene effects, the risk to develop elevated serum IgE (> 90th percentile) decreased by 80% while the risk to develop asthma dropped by 60%. Conclusion: These data indicate that only a combined analysis of various genetic alterations within the IL-4/IL-13 pathway reveals the development of atopy and asthma bronchiale.

Relationships between specific serum IgE, cytokines and polymorphisms in the IL‐4, IL‐4Rα in patients with penicillins allergy

Excessive production of interleukin (IL)-4, IL-13 and interferon (IFN)-gamma is thought to be important in the development of allergic disease and atopy. Several investigators have linked the IL-4 and IL-4R genes to allergic disease and atopy. The aim of this study is to further explore the mechanism of penicillins allergy and evaluate the possible role of the IL-4 C-589T and IL-4RalphaQ576R polymorphisms in modulating the allergic responses to penicillins. Radioallergosorbent test (RAST) was used to detect eight kinds of specific immunoglobulin E (IgE) to penicillins in serum. Serum levels of IL-4, IL-13 and IFN-gamma were measured by using enzyme-linked immunosorbent assay (ELISA). The IL-4 C-589T and IL-4RalphaQ576R polymorphisms were genotyped by polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP). Compared with control subjects, there were significantly higher levels of IL-4, IL-13 and IFN-gamma in allergic patients with positive specific IgE (P < 0.01), and the lower levels of IL-4 and IFN-gamma were observed in allergic patients with negative specific IgE (P < 0.05). We found a growing trend of IL-4 and IL-13 levels with the kind increasing of positive specific IgE, and even there were significant correlations between the three kinds of cytokines and many kinds of specific IgE (P < 0.05). The IL-4Ralpha*Q576 allele was significantly increased in patients with penicillins allergy compared with control subjects (P < 0.01). Furthermore, the allele was strongly associated with increased serum-specific benzylpenicilloyl (BPO)-, phenoxomethylpenicillanyl (PVA)- or ampicillanyl (APA)-IgE levels in patients with positive specific IgE (P < 0.05). These data suggest that IL-4, IL-13 and IFN-gamma play an important roles in penicillins allergy. The IL-4RalphaQ576R polymorphism may involve in the development of penicillins allergy, and through modulating specific serum IgE levels.