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• W2153235764 abstract "Recently in the Journal, Raedler et al1Raedler D. Illi S. Pinto L.A. von Mutius E. Illig T. Kabesch M. et al.IL10 polymorphisms influence neonatal immune responses, atopic dermatitis, and wheeze at age 3 years.J Allergy Clin Immunol. 2012; ([Epub ahead of print])Google Scholar published their interesting observations on the association between IL10 single nucleotide polymorphisms (SNPs) and markers of TH1/TH2 balance determined in cord blood samples of 200 healthy neonates.1Raedler D. Illi S. Pinto L.A. von Mutius E. Illig T. Kabesch M. et al.IL10 polymorphisms influence neonatal immune responses, atopic dermatitis, and wheeze at age 3 years.J Allergy Clin Immunol. 2012; ([Epub ahead of print])Google Scholar There was a significant association between 5 of the 8 studied genetic variations in the IL10 gene and TH2-oriented immune responses. For clinicians, the most interesting finding was a significant association between the same SNPs and the presence of atopic dermatitis, wheezing, or both at the age of 3 years.1Raedler D. Illi S. Pinto L.A. von Mutius E. Illig T. Kabesch M. et al.IL10 polymorphisms influence neonatal immune responses, atopic dermatitis, and wheeze at age 3 years.J Allergy Clin Immunol. 2012; ([Epub ahead of print])Google ScholarWe analyzed the IL10−1082 (rs1800896) AG SNP in 139 infants hospitalized for bronchiolitis at less than 6 months of age compared with 400 unselected blood donors.2Helminen M. Nuolivirta K. Virta M. Halkosalo A. Korppi M. Vesikari T. et al.IL-10 gene polymorphism at -1082 A/G is associated with severe rhinovirus bronchiolitis in infants.Pediatr Pulmonol. 2008; 43: 391-395Crossref PubMed Scopus (61) Google Scholar The cause of bronchiolitis was determined by using PCR in nasopharyngeal aspirates. We detected an overrepresentation of the AA genotype in 18 infants with bronchiolitis caused by viruses other than respiratory syncytial virus (RSV) compared with that seen in control subjects (66.7% vs 28.0%, P < .0001). Furthermore, 77.8% of 9 infants with bronchiolitis caused by rhinoviruses had the AA genotype (P < .001 vs control subjects). There were no significant differences between 98 RSV-positive infants and control subjects. These findings suggest different pathogenetic mechanisms for RSV-induced bronchiolitis and for bronchiolitis caused by other viruses, such as rhinoviruses. However, the IL10 polymorphism at −1082 was not associated with subsequent postbronchiolitis wheezing at 6 to 18 months of age.3Nuolivirta K. Hurme M. Halkosalo A. Koponen P. Korppi M. Vesikari T. et al.Gene polymorphism of IFNG +874 T/A and TLR4 +896 A/G and recurrent infections and wheezing in toddlers with history of bronchiolitis.Pediatr Infect Dis J. 2009; 28: 1121-1123Crossref PubMed Scopus (29) Google ScholarThe children were further followed up until the mean age of 6.4 years.4Koponen P. Helminen M. Paassilta M. Luukkaala T. Korppi M. Preschool asthma after bronchiolitis in infancy.Eur Respir J. 2012; 39: 76-80Crossref PubMed Scopus (90) Google Scholar, 5Koponen P, Qiushui H, Helminen M, Virta M, Korppi M. Carriage of the allele G at position -1082 of the IL10 promoter protects children from post-bronchiolitis asthma. Oral presentation at: the European Society Pediatric Infectious Diseases Annual Meeting 2012; May 9-11, 2012; Thessaloniki, Greece.Google Scholar Doctor-diagnosed asthma was present in only 1 (3.1%) of 32 of the children with the GG genotype at position −1082 of IL10 compared with 16 (15.0%) of 107 children with other genotypes (P = .04). Doctor-diagnosed asthma was present in 9 (13%) of 69 children with the AG genotype and 7 (21%) of 34 children with the AA genotype. The results suggest that carriage of the G allele at position −1082 of the IL10 gene might protect children against postbronchiolitic asthma. In addition, children with the AA genotype, which is known to be a low IL-10–producing genotype,6Nie W. Fang Z. Li B. Xiu Q.Y. Interleukin-10 promoter polymorphisms and asthma risk: A meta-analysis.Cytokine. 2012; 60: 849-855Crossref PubMed Scopus (37) Google Scholar seemed to be more likely to have preschool asthma, although the finding did not reach statistical significance.5Koponen P, Qiushui H, Helminen M, Virta M, Korppi M. Carriage of the allele G at position -1082 of the IL10 promoter protects children from post-bronchiolitis asthma. Oral presentation at: the European Society Pediatric Infectious Diseases Annual Meeting 2012; May 9-11, 2012; Thessaloniki, Greece.Google Scholar The findings are in line with observations that asthma is more common after rhinovirus-induced bronchiolitis than after RSV-induced bronchiolitis.7Kotaniemi-Syrjänen A. Vainionpää R. Reijonen T.M. Waris M. Korhonen K. Korppi M. Rhinovirus-induced wheezing in infancy—the first sign of childhood asthma?.J Allergy Clin Immunol. 2003; 111: 66-71Abstract Full Text Full Text PDF PubMed Scopus (349) Google ScholarThe polymorphism at IL10−1082 has been shown to affect IL-10 levels, and a recent meta-analysis of 18 case-control studies revealed a significant association between asthma susceptibility and the IL10−1082 AG polymorphism.6Nie W. Fang Z. Li B. Xiu Q.Y. Interleukin-10 promoter polymorphisms and asthma risk: A meta-analysis.Cytokine. 2012; 60: 849-855Crossref PubMed Scopus (37) Google Scholar The AA genotype carried a 1.27-fold (95% CI, 1.01-fold to 1.60-fold) asthma risk compared with the AG and GG genotypes,6Nie W. Fang Z. Li B. Xiu Q.Y. Interleukin-10 promoter polymorphisms and asthma risk: A meta-analysis.Cytokine. 2012; 60: 849-855Crossref PubMed Scopus (37) Google Scholar which is in line with our observations on preschool asthma after bronchiolitis in early infancy.According to HapMap data, the SNP rs1800896 included in our studies correlates completely (r2 = 1) or nearly completely (r2 = 0.96) with 2 SNPs (rs1800893 and rs1878672), associating with the outcomes in the study of Raedler et al.1Raedler D. Illi S. Pinto L.A. von Mutius E. Illig T. Kabesch M. et al.IL10 polymorphisms influence neonatal immune responses, atopic dermatitis, and wheeze at age 3 years.J Allergy Clin Immunol. 2012; ([Epub ahead of print])Google Scholar Thus the conclusions drawn from these SNPs are also applicable to the SNP rs1800896, and we agree with Raedler et al1Raedler D. Illi S. Pinto L.A. von Mutius E. Illig T. Kabesch M. et al.IL10 polymorphisms influence neonatal immune responses, atopic dermatitis, and wheeze at age 3 years.J Allergy Clin Immunol. 2012; ([Epub ahead of print])Google Scholar that IL10 polymorphisms play a critical role in early immune maturation, with potential effects on the development of wheezing and even on the development of asthma. Recently in the Journal, Raedler et al1Raedler D. Illi S. Pinto L.A. von Mutius E. Illig T. Kabesch M. et al.IL10 polymorphisms influence neonatal immune responses, atopic dermatitis, and wheeze at age 3 years.J Allergy Clin Immunol. 2012; ([Epub ahead of print])Google Scholar published their interesting observations on the association between IL10 single nucleotide polymorphisms (SNPs) and markers of TH1/TH2 balance determined in cord blood samples of 200 healthy neonates.1Raedler D. Illi S. Pinto L.A. von Mutius E. Illig T. Kabesch M. et al.IL10 polymorphisms influence neonatal immune responses, atopic dermatitis, and wheeze at age 3 years.J Allergy Clin Immunol. 2012; ([Epub ahead of print])Google Scholar There was a significant association between 5 of the 8 studied genetic variations in the IL10 gene and TH2-oriented immune responses. For clinicians, the most interesting finding was a significant association between the same SNPs and the presence of atopic dermatitis, wheezing, or both at the age of 3 years.1Raedler D. Illi S. Pinto L.A. von Mutius E. Illig T. Kabesch M. et al.IL10 polymorphisms influence neonatal immune responses, atopic dermatitis, and wheeze at age 3 years.J Allergy Clin Immunol. 2012; ([Epub ahead of print])Google Scholar We analyzed the IL10−1082 (rs1800896) AG SNP in 139 infants hospitalized for bronchiolitis at less than 6 months of age compared with 400 unselected blood donors.2Helminen M. Nuolivirta K. Virta M. Halkosalo A. Korppi M. Vesikari T. et al.IL-10 gene polymorphism at -1082 A/G is associated with severe rhinovirus bronchiolitis in infants.Pediatr Pulmonol. 2008; 43: 391-395Crossref PubMed Scopus (61) Google Scholar The cause of bronchiolitis was determined by using PCR in nasopharyngeal aspirates. We detected an overrepresentation of the AA genotype in 18 infants with bronchiolitis caused by viruses other than respiratory syncytial virus (RSV) compared with that seen in control subjects (66.7% vs 28.0%, P < .0001). Furthermore, 77.8% of 9 infants with bronchiolitis caused by rhinoviruses had the AA genotype (P < .001 vs control subjects). There were no significant differences between 98 RSV-positive infants and control subjects. These findings suggest different pathogenetic mechanisms for RSV-induced bronchiolitis and for bronchiolitis caused by other viruses, such as rhinoviruses. However, the IL10 polymorphism at −1082 was not associated with subsequent postbronchiolitis wheezing at 6 to 18 months of age.3Nuolivirta K. Hurme M. Halkosalo A. Koponen P. Korppi M. Vesikari T. et al.Gene polymorphism of IFNG +874 T/A and TLR4 +896 A/G and recurrent infections and wheezing in toddlers with history of bronchiolitis.Pediatr Infect Dis J. 2009; 28: 1121-1123Crossref PubMed Scopus (29) Google Scholar The children were further followed up until the mean age of 6.4 years.4Koponen P. Helminen M. Paassilta M. Luukkaala T. Korppi M. Preschool asthma after bronchiolitis in infancy.Eur Respir J. 2012; 39: 76-80Crossref PubMed Scopus (90) Google Scholar, 5Koponen P, Qiushui H, Helminen M, Virta M, Korppi M. Carriage of the allele G at position -1082 of the IL10 promoter protects children from post-bronchiolitis asthma. Oral presentation at: the European Society Pediatric Infectious Diseases Annual Meeting 2012; May 9-11, 2012; Thessaloniki, Greece.Google Scholar Doctor-diagnosed asthma was present in only 1 (3.1%) of 32 of the children with the GG genotype at position −1082 of IL10 compared with 16 (15.0%) of 107 children with other genotypes (P = .04). Doctor-diagnosed asthma was present in 9 (13%) of 69 children with the AG genotype and 7 (21%) of 34 children with the AA genotype. The results suggest that carriage of the G allele at position −1082 of the IL10 gene might protect children against postbronchiolitic asthma. In addition, children with the AA genotype, which is known to be a low IL-10–producing genotype,6Nie W. Fang Z. Li B. Xiu Q.Y. Interleukin-10 promoter polymorphisms and asthma risk: A meta-analysis.Cytokine. 2012; 60: 849-855Crossref PubMed Scopus (37) Google Scholar seemed to be more likely to have preschool asthma, although the finding did not reach statistical significance.5Koponen P, Qiushui H, Helminen M, Virta M, Korppi M. Carriage of the allele G at position -1082 of the IL10 promoter protects children from post-bronchiolitis asthma. Oral presentation at: the European Society Pediatric Infectious Diseases Annual Meeting 2012; May 9-11, 2012; Thessaloniki, Greece.Google Scholar The findings are in line with observations that asthma is more common after rhinovirus-induced bronchiolitis than after RSV-induced bronchiolitis.7Kotaniemi-Syrjänen A. Vainionpää R. Reijonen T.M. Waris M. Korhonen K. Korppi M. Rhinovirus-induced wheezing in infancy—the first sign of childhood asthma?.J Allergy Clin Immunol. 2003; 111: 66-71Abstract Full Text Full Text PDF PubMed Scopus (349) Google Scholar The polymorphism at IL10−1082 has been shown to affect IL-10 levels, and a recent meta-analysis of 18 case-control studies revealed a significant association between asthma susceptibility and the IL10−1082 AG polymorphism.6Nie W. Fang Z. Li B. Xiu Q.Y. Interleukin-10 promoter polymorphisms and asthma risk: A meta-analysis.Cytokine. 2012; 60: 849-855Crossref PubMed Scopus (37) Google Scholar The AA genotype carried a 1.27-fold (95% CI, 1.01-fold to 1.60-fold) asthma risk compared with the AG and GG genotypes,6Nie W. Fang Z. Li B. Xiu Q.Y. Interleukin-10 promoter polymorphisms and asthma risk: A meta-analysis.Cytokine. 2012; 60: 849-855Crossref PubMed Scopus (37) Google Scholar which is in line with our observations on preschool asthma after bronchiolitis in early infancy. According to HapMap data, the SNP rs1800896 included in our studies correlates completely (r2 = 1) or nearly completely (r2 = 0.96) with 2 SNPs (rs1800893 and rs1878672), associating with the outcomes in the study of Raedler et al.1Raedler D. Illi S. Pinto L.A. von Mutius E. Illig T. Kabesch M. et al.IL10 polymorphisms influence neonatal immune responses, atopic dermatitis, and wheeze at age 3 years.J Allergy Clin Immunol. 2012; ([Epub ahead of print])Google Scholar Thus the conclusions drawn from these SNPs are also applicable to the SNP rs1800896, and we agree with Raedler et al1Raedler D. Illi S. Pinto L.A. von Mutius E. Illig T. Kabesch M. et al.IL10 polymorphisms influence neonatal immune responses, atopic dermatitis, and wheeze at age 3 years.J Allergy Clin Immunol. 2012; ([Epub ahead of print])Google Scholar that IL10 polymorphisms play a critical role in early immune maturation, with potential effects on the development of wheezing and even on the development of asthma. IL10 polymorphisms influence neonatal immune responses, atopic dermatitis, and wheeze at age 3 yearsJournal of Allergy and Clinical ImmunologyVol. 131Issue 3PreviewIL10 encodes for IL-10, an important anti-inflammatory cytokine with pleiotropic effects. It is crucial for development of immune tolerance, downregulates expression of TH1 cytokines, and is relevant for T-cell regulation. Several IL10 single nucleotide polymorphisms (SNPs) were associated with inflammatory diseases, such as atopic diseases, which might have their onset during early immune maturation. Full-Text PDF ReplyJournal of Allergy and Clinical ImmunologyVol. 131Issue 1PreviewWe recently reported on the influence of IL10 polymorphisms on regulatory T cells and TH1/TH2 and proinflammatory cytokine secretion in cord blood and further development of immune-mediated diseases, such as atopic dermatitis and wheeze, later in childhood at the age of 3 years.1 We thank Koponen et al2 for the interest in our study and are encouraged to read about their results on a further IL10 promoter polymorphism (rs1800896), emphasizing the critical role of IL10 polymorphisms on immune regulation early in life. Full-Text PDF" @default.
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