The C11orf30-LRRC32 region is associated with total serum IgE levels in asthmatic patients.
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ABSTRACT:
SUBMITTER: Li X
PROVIDER: S-EPMC3268936 | biostudies-literature | 2012 Feb
REPOSITORIES: biostudies-literature
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The C11orf30-LRRC32 region is associated with total serum IgE levels in asthmatic patients.
Li Xingnan X Ampleford Elizabeth J EJ Howard Timothy D TD Moore Wendy C WC Li Huashi H Busse William W WW Castro Mario M Erzurum Serpil C SC Fitzpatrick Anne M AM Gaston Benjamin B Israel Elliot E Jarjour Nizar N NN Teague W Gerald WG Wenzel Sally E SE Hawkins Gregory A GA Bleecker Eugene R ER Meyers Deborah A DA
The Journal of allergy and clinical immunology 20111108 2
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Project description:SOCS-1 is a critical regulator of multiple signaling pathways, including those activated by cytokines that regulate Ig H chain class switching to IgE. Analysis of mice with mutations in the SOCS-1 gene demonstrated that IgE levels increase with loss of SOCS-1 alleles. This suggested that overall SOCS-1 acts as an inhibitor of IgE expression in vivo. A genetic association study was performed in 474 children enrolled in the Tucson Children's Respiratory Study to determine if genetic variation in the SOCS-1 locus correlates with altered levels of IgE. Carriers of the C-allele for a novel, 3' genomic single nucleotide polymorphism (SNP) in the SOCS-1 gene (SOCS1+1125G > C; rs33932899) were found to have significantly lower levels of serum IgE compared with those of homozygotes for the G-allele. Analysis demonstrated that the SOCS1+1125G > C SNP was in complete linkage disequilibrium with an SNP at position SOCS1-820G > T (rs33977706) of the SOCS-1 promoter. Carriers of the T-allele at the SOCS1-820G > T were also found to be associated with the decreased IgE. The promoter SNP increased transcriptional activity of the SOCS-1 promoter in reporter assays and human B cells. Consistent with this observation, the presence of this polymorphism within the promoter abolished binding of yin yang-1, which is identified as a negative regulator of SOCS-1 transcriptional activity. These data suggest that genetic variation in the SOCS-1 promoter may affect IgE production.
| S-EPMC3159751 | biostudies-literature
Project description:Total serum immunoglobulin E (IgE) is elevated in multiple allergic diseases and is considered a good predictor of atopy. Several studies have been performed on the association of IgE levels with the polymorphism of the ADAM33 gene in asthmatic patients. The aim of this study was to determine whether there is an association between IgE levels and the genetic polymorphisms of the ADAM33 gene (T1, T2, T + 1, V4, S1, S2, and Q-1) in both healthy and asthmatic patients among Jordanians. The clinical data were collected for this case-control study from 267 asthmatic patients and 225 control subjects. Seven genetic polymorphisms (T1, T2, T + 1, V4, S1, S2, and Q-1) of the gene ADAM33 were analyzed using the polymerase chain reaction/restriction fragment length polymorphism method. The minor alleles (G) of T1, (A) of T2, T + 1, and (G) of V4 polymorphisms were associated with a significant increase in total serum IgE levels in adults but not children. The V4 genetic polymorphism, however, showed a significant association with IgE levels in both adults and children. The S1 polymorphism was significantly associated with the codominant module only in the adults. The S2 polymorphism showed a significant association (p-value < 0.05) in both codominant and recessive models. However, in the dominant model for both pediatric control and asthmatic patients, the association between the IgE and S2 polymorphism was insignificant (p-value = 0.7271 and 0.5259, respectively). This study found a statistically significant association between multiple ADAM33 genetic polymorphisms and IgE levels. Such findings add to the growing evidence that the ADAM33 gene has a major impact on IgE levels among asthmatic patients of Jordanian origin.
| S-EPMC8146671 | biostudies-literature
Project description:Immunoglobulin E (IgE) serves a crucial role in the pathogenesis of several allergic disorders, and elevated levels of total serum IgE have been associated with asthma. IgE is responsible for the release of several asthma-associated inflammatory mediators from mast cells, such as histamine and prostaglandins. The aim of the present study was to assess the association of interleukin (IL)-13 single nucleotide polymorphism (SNP) rs20541 and forkhead box O3a (FOXO3a) SNP rs13217795 with IgE levels in asthmatic patients and a healthy control group. Genetic polymorphism analysis of SNPs was performed using PCR/restriction fragment length polymorphism. Total serum IgE levels were measured using an ELISA kit. Genotypes were grouped into three models: Co-dominant, dominant and recessive. Major and minor alleles for IL-13 SNP rs20541 and FOXO3a SNP rs13217795 were C and T, whereas for IL-13, they were G and A, respectively. There was a significant association between the IL-13 rs20541 SNP and the total IgE serum levels, in which pure minor alleles were associated with a significant reduction (~5x lower) in IgE serum levels compared with the major alleles in asthmatic subjects and to a lesser extent in the control subjects. Additionally, the FOXO3a rs13217795 SNP was associated with a significant increase in total IgE levels (~5x higher) in the asthmatic patients compared with the control subjects. In conclusion, the present study confirmed that there was a significant association between the IL-13 SNP rs20541 and asthma, and an association between the FOXO3a SNP rs13217795 with asthma pathogenicity in Jordanian subjects.
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Project description:BackgroundEotaxin (CCL11) is a small protein produced in the lungs of patients with asthma, and is a potent chemoattractant for eosinophils.AimTo elucidate the role of eotaxin in asthma by an association study of functional and novel eotaxin polymorphisms in case-control and family-based study designs.MethodsEotaxin +67G/A, -384A/G and -426C/T single-nucleotide polymorphisms and a hexanucleotide (GAAGGA)(n) repeat 10.9 kb upstream of the gene were genotyped in a cohort of age, sex and ethnically matched patients with asthma (n = 235) and healthy controls (n = 239), and also in a study population of 230 families with asthma recruited from north/northwest India. Total serum IgE (TsIgE) and plasma eotaxin levels were measured using ELISA.Results+67G/A polymorphism was found to be significantly associated with asthma in case-control (p = 0.009) and family-based studies (p = 0.006). Its functional role, as it was correlated with plasma eotaxin levels (p = 0.006), was also demonstrated. Further, -384C/T single-nucleotide polymorphism was found to be significantly associated with log(10) TsIgE (p = 0.016 in case-control and p = 0.018 in families) and eotaxin levels (p = 0.007). Most interestingly, for the first time, a highly significant association of the newly studied (GAAGGA)(n) hexanucleotide repeat with asthma (p = 3x10(-6)), log(10)TsIgE (p = 0.006) and eotaxin levels (p = 0.004) was observed. G_A_C_8 was also identified as an important risk haplotype associated with high TsIgE and plasma eotaxin levels.ConclusionsThis study provides further evidence that eotaxin polymorphisms are associated with the development of asthma by regulating eotaxin levels and reinforces towards the scanning of other chemokine genes present at 17q21 locus for their association with asthma and related phenotypes.
| S-EPMC2740889 | biostudies-literature
Project description:High levels of serum IgE are considered markers of parasite and helminth exposure. In addition, they are associated with allergic disorders, play a key role in anti-tumoral defence, and are crucial mediators of autoimmune diseases. Total IgE is a strongly heritable trait. In a genome-wide association study (GWAS), we tested 353,569 SNPs for association with serum IgE levels in 1,530 individuals from the population-based KORA S3/F3 study. Replication was performed in four independent population-based study samples (total n = 9,769 individuals). Functional variants in the gene encoding the alpha chain of the high affinity receptor for IgE (FCER1A) on chromosome 1q23 (rs2251746 and rs2427837) were strongly associated with total IgE levels in all cohorts with P values of 1.85 x 10(-20) and 7.08 x 10(-19) in a combined analysis, and in a post-hoc analysis showed additional associations with allergic sensitization (P = 7.78 x 10(-4) and P = 1.95 x 10(-3)). The "top" SNP significantly influenced the cell surface expression of FCER1A on basophils, and genome-wide expression profiles indicated an interesting novel regulatory mechanism of FCER1A expression via GATA-2. Polymorphisms within the RAD50 gene on chromosome 5q31 were consistently associated with IgE levels (P values 6.28 x 10(-7)-4.46 x 10(-8)) and increased the risk for atopic eczema and asthma. Furthermore, STAT6 was confirmed as susceptibility locus modulating IgE levels. In this first GWAS on total IgE FCER1A was identified and replicated as new susceptibility locus at which common genetic variation influences serum IgE levels. In addition, variants within the RAD50 gene might represent additional factors within cytokine gene cluster on chromosome 5q31, emphasizing the need for further investigations in this intriguing region. Our data furthermore confirm association of STAT6 variation with serum IgE levels.
| S-EPMC2565692 | biostudies-literature
Project description:Background: High total IgE levels are weak predictors of T2High and have been reported in nonallergic asthma. Therefore, the role of total serum IgE (IgE) in the T2High phenotype is still debated. Objective: This study investigated the reliability of stratifying asthmatics into IgEHigh and IgELow within the T2High and T2Low phenotypes. Methods: This cross-sectional single-center study investigated the association of clinical, functional, and bio-humoral parameters in a large asthmatic population stratified by IgE ≥ 100 kU/L, allergen sensitization, B-EOS ≥ 300/µL, and FENO ≥ 30 ppb. Results: Combining T2 biomarkers and IgE identifies (1) T2Low-IgELow (15.5%); (2) T2Low-IgEHigh (5.1%); (3) T2High-IgELow (33.6%); and T2High-IgEHigh (45.7%). T2Low-IgELow patients have more frequent cardiovascular and metabolic comorbidities, a higher prevalence of emphysema, and higher LAMA use than the two T2High subgroups. Higher exacerbation rates, rhinitis, and anxiety/depression syndrome characterize the T2Low-IgEHigh phenotype vs. the T2Low-IgELow phenotype. Within the T2High, low IgE was associated with female sex, obesity, and anxiety/depression. Conclusions: High IgE in T2Low patients is associated with a peculiar clinical phenotype, similar to T2High in terms of disease severity and nasal comorbidities, while retaining the T2Low features. IgE may represent an additional biomarker for clustering asthma in both T2High and T2Low phenotypes rather than a predictor of T2High asthma "per se".
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Project description:Abnormalities in the human microbiota are associated with the etiology of allergic diseases. Although disease site-specific microbiota may be associated with disease pathophysiology, the role of the nasal microbiota is unclear. We sought to characterize the microbiota of the site of allergic rhinitis, the inferior turbinate, in subjects with allergic rhinitis (n = 20) and healthy controls (n = 12) and to examine the relationship of mucosal microbiota with disease occurrence, sensitized allergen number, and allergen-specific and total IgE levels. Microbial dysbiosis correlated significantly with total IgE levels representing combined allergic responses but not with disease occurrence, the number of sensitized allergens, or house dust mite allergen-specific IgE levels. Compared to the populations in individuals with low total IgE levels (group IgElow), low microbial biodiversity with a high relative abundance of Firmicutes phylum (Staphylococcus aureus) and a low relative abundance of Actinobacteria phylum (Propionibacterium acnes) was observed in individuals with high total serum IgE levels (group IgEhigh). Phylogeny-based microbial functional potential predicted by the 16S rRNA gene indicated an increase in signal transduction-related genes and a decrease in energy metabolism-related genes in group IgEhigh as shown in the microbial features with atopic and/or inflammatory diseases. Thus, dysbiosis of the inferior turbinate mucosa microbiota, particularly an increase in S. aureus and a decrease in P. acnes, is linked to high total IgE levels in allergic rhinitis, suggesting that inferior turbinate microbiota may be affected by accumulated allergic responses against sensitized allergens and that site-specific microbial alterations play a potential role in disease pathophysiology.
| S-EPMC5865026 | biostudies-literature
Project description:There are few studies addressing the longitudinal analysis of serum IgE levels and its impact to the development of atopic diseases in early childhood. We investigated 170 children who regularly followed up at our clinic for 4 years in a birth cohort study with at least 3 time-points of serum samples. The pattern of total serum IgE levels from 6 months to 4 years of age was clustered using K-means method in R software. Specific immunoglobulin E antibodies against food (egg white and milk) and inhalant allergens (D. pteronyssinus and D. farinae) were measured at 0.5, 1, 1.5, 2, 3 and 4 years of age. By using K-means clustering, the dynamic changes in serum IgE levels was significantly stratified into 3 clusters (cluster A, < 100 kU/L, n = 106; cluster B, 100-200 kU/L, n = 35; cluster C, ≥ 200 kU/L, n = 29). A persistent total IgE levels higher than 100 kU/L appeared to be associated with higher prevalence of sensitization to food but not mite. However, a persistent IgE levels higher than 200 kU/L was not only remarkably related to increased prevalence of mite sensitization, but also risk of eczema at age 1 and allergic rhinitis and asthma at age 2, 3 and 4. In conclusion, a persistent total serum IgE level ≥ 200 kU/L since infancy is strongly associated with the presence of food and mite sensitization, as well as the development of eczema in infants, and rhinitis and asthma later in early childhood.
| S-EPMC7718260 | biostudies-literature
Project description:BackgroundIgE bound on the surface of mast cells contributes to the pathogenesis of chronic spontaneous urticaria (CSU). Atopy is a predisposing factor for CSU, where omalizumab is a widely used monoclonal antibody to control urticaria symptoms via capturing serum free IgE. However, the role of serum free IgE is not clarified in CSU. The present study evaluated the clinical relevance of serum free IgE in patients with CSU.MethodsEighty-eight patients with CSU and 76 healthy controls (HCs) were enrolled in this study. Serum total and Dermatophagoides pteronyssinus (Der p)-specific IgE levels were measured by ImmunoCAPs. The serum free IgE levels were measured by ELISA using a novel IgETRAP, and their associations with clinical parameters, including urticaria activity score (UAS), were evaluated. Changes in serum free and total IgE levels after omalizumab treatment were observed in 23 CSU patients in comparison between responders (≥50% reduction in UAS) and non-responders (<50% reduction).ResultsSignificantly higher serum free/total IgE levels were noted in CSU patients than in HCs with a positive correlation between the 2 values (rho = 0.87, P < 0.001). Among CSU patients, atopics had significantly higher serum free IgE levels than non-atopics, while no associations were noted with UAS, urticaria duration, or the results of serum ANA or autologous serum skin tests. In addition, there were no significant changes in serum free IgE levels during 12 months of omalizumab treatment. No significant differences were noted in serum free/total IgE levels or clinical parameters between responders and non-responders, while responders have higher serum Der p-specific IgE level and its ratio to serum free/total IgE level than non-responders (P < 0.05, respectively).ConclusionsThese findings suggest that increased serum free IgE may be involved in the development of CSU by activating mast cells, especially in atopics. High Der p-specific IgE level and its ratio to serum free IgE level may be a potential biomarker for predicting favorable responses to omalizumab in CSU.
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