Patterns of GATA3 and IL13 gene polymorphisms associated with childhood rhinitis and atopy in a birth cohort

Huebner, Marianne; Kim, Dong Yun; Ewart, Susan; Karmaus, Wilfried; Sadeghnejad, Alireza; Arshad, Syed Hasan

doi:10.1016/j.jaci.2007.09.020

Cited by 22 publications

(17 citation statements)

References 31 publications

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“…Finally, we found a borderline association between IL13 rs1800925 and the risk to develop allergic rhinitis, confirming the data reported by Huebner et al (21) in a cohort of 923 children and by Black et al (22) in the longitudinal 1946 birth cohort study of the UK Medical Research Council's National Survey of Health and Development. 0, 1, and 2 represent the number of major, heterozygote and minor genotypes, respectively.…”

Section: Discussionsupporting

confidence: 91%

Polymorphisms in IL13 pathway genes in asthma and chronic obstructive pulmonary disease

Beghè¹,

Hall²,

Parker³

et al. 2010

Allergy

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Asthma and chronic obstructive pulmonary disease (COPD) are chronic inflammatory respiratory diseases that are most likely due to an interaction between genetic and environmental factors. Atopy is the most important risk factor of asthma (1) and tobacco smoking is the most important risk factor of COPD (2).Interleukin-13 (IL13) is a Th2 cytokine implicated in (i) recruitment of inflammatory cells from the blood to the lung, (ii) immunoglobulin (Ig) E production by B cells, (iii) regulation of matrix metalloproteinases and (iv) induction of mucin production and secretion (3, 4). IL13 is produced by a variety of cells, including Th2 CD4 + , Th1 CD4 + , CD8 + T cells, mast cells, basophils and eosinophils. IL13 mediates its effects by interacting with a complex receptor system comprising an IL4Ra/IL13Ra1 heterodimer and the IL13Ra2 receptor (3).The involvement of IL13 in the pathogenesis of asthma has been extensively documented (3-5). The administration of recombinant IL13 in the lungs of mice increases airway AbstractBackground: Asthma and chronic obstructive pulmonary disease (COPD) are chronic respiratory diseases involving an interaction between genetic and environmental factors. Interleukin-13 (IL13) has been suggested to have a role in both asthma and COPD. We investigated whether single nucleotide polymorphisms (SNPs) in the IL13 pathway may contribute to the susceptibility and severity of asthma and COPD in adults. Methods: Twelve SNPs in IL13 pathway genes -IL4, IL13, IL4RA, IL13RA1, IL13RA2 and STAT6 -were genotyped in subjects with asthma (n = 299) and in subjects with COPD or healthy smokers (n = 992). Genetic association was evaluated using genotype and allele models for asthma severity, atopy phenotypes and COPD susceptibility. Linear regression was used to determine the effects of polymorphism on baseline lung function (FEV 1 , FEV 1 /FVC). Results: In asthmatics, three IL13 SNPs -rs1881457(-1512), rs1800925(-1111) and rs20541(R130Q) -were associated with atopy risk. One SNP in IL4RA1 [rs1805010(I75V)] was associated with asthma severity, and several IL13 SNPs showed borderline significance. IL13 SNPs rs1881457(-1512) and rs1800925 (-1111) were associated with better FEV 1 and FEV 1 /FVC in asthmatics. IL13 SNPs rs2066960(intron 1), rs20541(R130Q) and rs1295685(exon 4) were associated with COPD risk and lower baseline lung function in the recessive model. In females, but not in males, rs2250747 of the IL13RA1 gene was associated with COPD and lower FEV 1 . Conclusion: These data suggest that IL13 SNPs (promoter and coding region) and, to a lesser extent, IL4RA SNPs may contribute to atopy and asthma. We also provide tentative evidence that IL13 SNPs in the coding region may be of significance in COPD susceptibility.

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Section: Discussionsupporting

confidence: 91%

Polymorphisms in IL13 pathway genes in asthma and chronic obstructive pulmonary disease

Beghè¹,

Hall²,

Parker³

et al. 2010

Allergy

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“…14 IL-1312044G/A (rs20541) is a single nucleotide polymorphism (SNP) in the coding region of this gene; expression of this IL13 variant was associated with asthma, 15,16 atopy, 17 and increased total serum IgE levels in a birth cohort. Previous studies of IL13 polymorphisms and AR reported that SNPs in GATA3 (rs105820) and IL13 (rs1800925) interacted to affect the risk for AR 18 ; this same IL13 polymorphism was associated with the development of AR in our study of a Korean population. 19 We investigated whether the IL1312044G/A polymorphism interacts with environmental factors to affect the risk for AR.…”

supporting

confidence: 66%

Interaction between IL13 genotype and environmental factors in the risk for allergic rhinitis in Korean children

Kim

Kwon

Seo

et al. 2012

Journal of Allergy and Clinical Immunology

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“…Several studies have addressed a possible genetic interaction between SNPs of the IL13 and IL4R gene, yet with different asthma and allergic phenotypes and variable polymorphisms [22,23,24,25], or with other genes [26,27]. The odds ratio for asthma in the current study was greater with polymorphisms Arg130Gln and Glu375Ala than with the polymorphisms C–1111T and Ser478Pro, suggesting an additive effect.…”

Section: Discussionmentioning

confidence: 51%

Interleukin 13 and Interleukin 4 Receptor-α Polymorphisms in Rhinitis and Asthma

Bottema

Nolte

Howard

et al. 2010

Int Arch Allergy Immunol

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Background: Asthma and rhinitis may represent two manifestations of the same airway disease. Genetic research can increase our understanding of their common or distinct pathogenesis. IL13 and IL4R polymorphisms are associated with asthma and show gene-gene interaction in asthma. Their role in rhinitis has not been extensively studied. Methods: Association of IL13 and IL4R polymorphisms in relation to rhinitis, asthma, serum IgE and skin test response was studied in: (1) 188 trios ascertained through a proband with rhinitis who were clinically not affected by asthma; (2) 407 trios with an asthmatic proband, and (3) 118 asthma cases and 102 unrelated healthy controls using family-based association testing, logistic regression, and analysis of variance as appropriate. Gene-gene interaction was evaluated using logistic regression analysis. Results: IL13 C–1111T (rs1800925) was significantly associated with rhinitis and atopic phenotypes in rhinitis trios that were not affected by clinical asthma. IL13 Arg130Gln (rs20541) and G870A (rs1295685) were consistently associated with asthma and serum IgE in both asthma populations. IL4R Glu375Ala (rs1805011) and Ser411Leu (rs1805013) were associated with asthma in the asthma case-control population. Combining risk genotypes of IL13 Arg130Gln with IL4R Glu375Ala, and IL13 C–1111T with IL4R Ser478Pro yielded increased risks for asthma compared to their separate effects. Conclusion:IL13 polymorphisms were associated with asthma and rhinitis without clinical asthma; thus, these polymorphisms may constitute a common etiologic pathway for their development. In addition, the study replicates a previously reported interaction of IL13 and IL4R polymorphisms in asthma.

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Patterns of GATA3 and IL13 gene polymorphisms associated with childhood rhinitis and atopy in a birth cohort

Abstract: Background-GATA3 activates transcription of the T H 2 cytokines, including IL13, an important step in the allergic inflammatory pathway.

Cited by 22 publications

References 31 publications

Polymorphisms in IL13 pathway genes in asthma and chronic obstructive pulmonary disease

Polymorphisms in IL13 pathway genes in asthma and chronic obstructive pulmonary disease

Interaction between IL13 genotype and environmental factors in the risk for allergic rhinitis in Korean children

Interleukin 13 and Interleukin 4 Receptor-α Polymorphisms in Rhinitis and Asthma

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