Unraveling the complex genetic underpinnings of asthma and allergic disorders

Swarr, Daniel T.; Hákonarson, Hákon

doi:10.1097/aci.0b013e32833da71d

Cited by 17 publications

(7 citation statements)

References 88 publications

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“…Before the advent of genome-wide association studies (GWAS) [8], almost a thousand candidate-gene association studies for asthma and related traits were published [9]. Considering the gene as the unit of replication and using a broad definition for asthma, Ober & Hoffjan [5] elegantly summarized the accumulated evidence for candidate-gene association studies from the literature by assessing the consistency of findings [10].…”

Section: Introductionmentioning

confidence: 99%

Assessing the Validity of Asthma Associations for Eight Candidate Genes and Age at Diagnosis Effects

et al. 2013

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BackgroundBefore the advent of genome-wide association studies (GWAS), ADAM33, ADRB2, CD14, MS4A2 (alias FCER1B), IL13, IL4, IL4R, and TNF constituted the most replicated non-HLA candidate genes with asthma and related traits. However, except for the IL13-IL4 region, none of these genes have been found in close proximity of genome-wide significant hits among GWAS for asthma or related traits. Here we aimed to assess the reproducibility of these asthma associations and to test if associations were more evident considering the effect of age at diagnosis.Methodology/Principal FindingsWe systematically evaluated 286 common single nucleotide polymorphisms (SNPs) of these 8 genes in a sample of 1,865 unrelated Spanish individuals (606 asthmatics and 1,259 controls). We found that variants at MS4A2, IL4R and ADAM33 genes demonstrated varying association effects with the age at diagnosis of asthma, with 10 SNPs showing study-wise significance after the multiple comparison adjustment. In addition, in silico replication with GWAS data supported the association of IL4R.Conclusions/SignificanceOur results support the important role of MS4A2, IL4R and ADAM33 genes in asthma and/or atopy susceptibility. However, additional studies in larger samples sets are needed to firmly implicate these genes in asthma susceptibility, and also to identify the causal variation underlying the associations found.

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Section: Introductionmentioning

confidence: 99%

Assessing the Validity of Asthma Associations for Eight Candidate Genes and Age at Diagnosis Effects

et al. 2013

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“…This could explain the significant impact of viruses and bacteria in acute asthma exacerbations [71,72]. The expensive genome-wide association (GWA) studies have yielded several hypothesis-free candidate genes with known or suspected links to epithelial barrier functions for further analyses in allergic diseases [73,74]. Finally novel approaches pursuing to measure epithelial proteomics [75] and lipidomics [76] will become possible in near future thus allowing us to broaden the DNA and mRNA based GWA analyses.…”

Section: Discussionmentioning

confidence: 99%

Allergy as an epithelial barrier disease

Mattila

Joenväära

Renkonen

et al. 2011

Clinical & Translational All

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The objective of this review is to focus on putative modified epithelial functions related to allergy. The dysregulation of the epithelial barrier might result in the allergen uptake, which could be the primary defect in the pathogenesis of allergic reaction. We review the literature of the role of respiratory epithelium as an active barrier, how allergens are transported through it and how it senses the hostile environmental allergens and other dangerous stimuli.

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“…Several family-based studies provide evidence that AA and AR are multifactorial diseases induced by gene-environment interactions [42]. During the past decade, asthma susceptibility genes have been identified by genome-wide searches and candidate gene studies.…”

Section: Genetic Linkage Studies Suggest That Complement Contributes mentioning

confidence: 99%

The Role of Complement in the Diagnosis and Management of Allergic Rhinitis and Allergic Asthma

Laumonnier

Schmudde

Köhl

2010

Curr Allergy Asthma Rep

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Allergic rhinitis and asthma are common chronic inflammatory diseases of the nasal mucus membranes and the upper airways with a high prevalence in Western countries. In addition to maladaptive T-helper type 2 (Th2) immunity, Th17 cells can drive the inflammatory responses in both diseases. Several reports have shown that the complement system is activated locally and systemically in allergic rhinitis and/or allergic asthma patients. Importantly, recent findings in experimental models of allergic rhinitis and allergic asthma suggest that the complement cleavage products complement 3a and complement 5a and the activation of their corresponding receptors in antigen-presenting cells regulate the development of maladaptive Th2 and Th17 immunity. These findings in experimental asthma are corroborated by genome-wide searches and candidate gene studies in humans. We discuss recent findings in experimental and human allergic airway diseases suggesting that complement may serve as a new diagnostic and therapeutic target for both disorders.

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Unraveling the complex genetic underpinnings of asthma and allergic disorders

Cited by 17 publications

References 88 publications

Assessing the Validity of Asthma Associations for Eight Candidate Genes and Age at Diagnosis Effects

Assessing the Validity of Asthma Associations for Eight Candidate Genes and Age at Diagnosis Effects

Allergy as an epithelial barrier disease

The Role of Complement in the Diagnosis and Management of Allergic Rhinitis and Allergic Asthma

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