Chromosome 17q21 Gene Variants Are Associated with Asthma and Exacerbations but Not Atopy in Early Childhood

Bisgaard, Hans; Bønnelykke, Klaus; Sleiman, Patrick; Brasholt, Martin; Chawes, Bo; Kreiner‐Møller, Eskil; Stage, Malene; Kim, Cecilia; Tavendale, Roger; Baty, Florent; Pipper, Christian Bressen; Palmer, Colin N.A.; Hakonarsson, Hakon

doi:10.1164/rccm.200809-1436oc

Cited by 195 publications

(182 citation statements)

References 40 publications

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“…Analyses by the GABRIEL consortium revealed no association between the ORMDL3/GSDMB locus and IgE levels, a commonly used indicator for atopy (11). This has been replicated in numerous studies (8,9,13,18,22,23). The absence of any overlap between the most highly associated asthma-susceptible SNPs and serum IgE at any locus tested suggests separate, genetically distinct pathways.…”

Section: Association Of the 17q21 Locus With Asthma Typesmentioning

confidence: 79%

17q21 locus and ORMDL3: an increased risk for childhood asthma

Ono

Worgall

2013

Pediatr Res

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Section: Association Of the 17q21 Locus With Asthma Typesmentioning

confidence: 79%

17q21 locus and ORMDL3: an increased risk for childhood asthma

Ono

Worgall

2013

Pediatr Res

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“…6 rs7216389 is located in an intron of the GSDMB gene (encoding the gasdermin-like protein), but its association with asthma was originally linked to the expression of the nearby ORMDL3 gene (encoding the ORM1-like 3 protein). Subsequent reports have provided further support for the association of this 17q21 locus with childhood [7][8][9][10][11] and persistent asthma, 12 but the mechanisms underlying this effect remain unclear.…”

Section: Introductionmentioning

confidence: 99%

A sequence variant on 17q21 is associated with age at onset and severity of asthma

et al. 2010

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A sequence variant (rs7216389-T) near the ORMDL3 gene on chromosome 17q21 was recently found to be associated with childhood asthma. We sought to evaluate the effect of rs7216389-T on asthma subphenotypes and its correlation with expression levels of neighboring genes. The association of rs7216389-T with asthma was replicated in six European and one Asian study cohort (N¼4917 cases N¼34 589 controls). In addition, we found that the association of rs7216389-T was confined to cases with early onset of asthma, particularly in early childhood (age: 0-5 years OR¼1.51, P¼6.89 . 10 À9 ) and adolescence (age: 14-17 years OR¼1.71, P¼5.47 . 10 À9 ). A weaker association was observed for onset between 6 and 13 years of age (OR¼1.17, P¼0.035), but none for adult-onset asthma (OR¼1.07, P¼0.12). Cases were further stratified by sex, asthma severity and atopy status. An association with greater asthma severity was observed among early-onset asthma cases (P¼0.0012), but no association with sex or atopy status was observed among the asthma cases. An association between sequence variants and the expression of genes in the 17q21 region was assessed in white blood cell RNA samples collected from Icelandic individuals (n¼743). rs7216389 associated with the expression of GSDMB and ORMDL3 genes. However, other sequence variants showing a weaker association with asthma compared with that of rs7216389 were more strongly associated with the expression of both genes. Thus, the contribution of rs7216389-T to the development of asthma is unlikely to operate only through an impact on the expression of ORMDL3 or GSDMB genes.

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“…There is emerging evidence that the innate immune response in asthma is impaired, airway inflammation may modulate the response to triggers and genetic polymorphisms may confer an increased risk of exacerbations [24]. Because it has been already suggested that the presence of eosinophilic inflammation in the bronchial wall promotes the development of an exacerbation in combination with a viral infection, a clinical research study concerning the eosinophil response in the bronchial wall to S. commune or to the secretory products of this fungus will also be important to elucidate the mechanisms underlying the exacerbation of asthma in the future.…”

Section: Discussionmentioning

confidence: 99%

The Influence of Schizophyllum commune on Asthma Severity

Ogawa

Fujimura

Takeuchi

et al. 2011

Lung

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The sensitization and exposure to fungal allergens have been reported to be associated with asthma. The aim of this study was to clarify the impact of sensitization to Schizophyllum commune (S. commune) on the severity and exacerbations of asthma.Ninety-two patients with asthma of various levels of severity (mild (n=18), moderate (28), and severe (46)) and exacerbation severity (moderate (n=43) and severe (6)), were retrospectively examined with regard to fungal sensitization such as specific IgE or intradermal skin reactions against S. commune and other common allergens. We also classified the patients into 3 groups; 1) 3 or more asthma attacks during the past 1 year (F-BA) (n=29), 2) one or two asthma attacks (NF-BA) (n=20), and 3) no asthma attack (C-BA) (n=43).The positive rate of late cutaneous reactions to S. commune was higher in patients with severe asthma (41.2%) than moderate (26.1%) and mild asthma (6.7%), and was significantly different among the three groups (p<0.05). Though the ratio did not show significant difference between the patients having a severe (83.3%) and moderate (36.1%) exacerbation, it was higher in F-BA (60.9 %) than in NF-BA (21.1%) and C-BA patients (10.0%), and it was significantly different among the three groups (p=0.0002). A multivariate analysis identified positive results for late phase skin 4 reactions to S. commune and the age of the patients as an independent determinant of asthma severity, and the skin results and %FVC an independent determinant of exacerbation frequency.This study demonstrated that S. commune is an environmental fungus that appears to enhance both the severity of asthma and the exacerbation frequency.

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Chromosome 17q21 Gene Variants Are Associated with Asthma and Exacerbations but Not Atopy in Early Childhood

Cited by 195 publications

References 40 publications

17q21 locus and ORMDL3: an increased risk for childhood asthma

17q21 locus and ORMDL3: an increased risk for childhood asthma

A sequence variant on 17q21 is associated with age at onset and severity of asthma

The Influence of Schizophyllum commune on Asthma Severity

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