Genetics of Asthma and Allergic Diseases

Haider, Sadia; Simpson, Angela; Čustović, Adnan

doi:10.1007/164_2021_484

Cited by 8 publications

(5 citation statements)

References 122 publications

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“…No organic disease (Tamari and Hirota, 2014). Voluntary acceptance of disease-related questionnaires (Haider et al, 2022). No participation in any drug clinical trials within 3 months.…”

Section: Study Design and Participantsmentioning

confidence: 99%

“…Allergy and associated illnesses are strongly heritable. Genetic vulnerability to allergy illnesses may be considerably influenced by disease-related single nucleotide polymorphisms (SNPs), according to genome-wide association studies (GWAS) (Tamari and Hirota, 2014;Bønnelykke et al, 2015;Haider et al, 2022). Studies of monogenic disorders have uncovered important cellular processes and protein roles in allergies.…”

Section: Introductionmentioning

confidence: 99%

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The 4G/5G polymorphism of plasminogen activator inhibitor type 1 is a predictor of allergic cough

Tang

Lyu²,

Li³

et al. 2023

Front. Genet.

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Background: It has been suggested that genetic factors may be substantially linked to allergy disorders. This study aims to investigate the relationship between the genetic susceptibility of Chinese patients with allergy disorders and the polymorphisms of plasminogen activator inhibitor 1 gene (PAI-1) rs1799762, cysteinyl leukotriene receptor 1 gene (CYSLTR1) rs320995, gasdermin B gene (GSDMB) rs7216389, glycoprotein IIIa gene (GPIIIa) rs5918, glycoprotein Ib alpha gene (GP1BA) rs6065, platelet endothelial aggregation receptor 1 gene (PEAR1) rs12041331, and tumor necrosis factor alpha gene (TNF-α) rs1800629.Methods: From the Peking Union Medical College Hospital, this study enrolled 60 healthy participants and 286 participants with allergic diseases. TaqMan-minor groove binder (MGB) quantitative polymerase chain reaction (qPCR) was used to examine the gene polymorphisms in each group.Results: The TaqMan-MGB qPCR results were completely consistent with the DNA sequencing results, according to other studies in this medical center (Kappa = 1, p < .001). Only the distribution of PAI-1 rs1799762 was different between patients with allergic cough and healthy people (χ2 = 7.48, p = .0238). With regard to cough patients, the 4G4G and 5G5G genotypes were more frequent (allergic cough vs. healthy individuals: 4G4G 57.9% vs. 26.7%; 5G5G 20.0% vs. 13.3%), but the 4G5G genotype was more frequent in healthy people (allergic cough vs. healthy individuals: 45.7% vs. 60.0%). The CYSLTR1 rs320995, GSDMB rs7216389, GPIIIa rs5918, GP1BA rs6065, PEAR1 rs12041331, and TNF-α rs1800629 polymorphisms, however, did not show any of such relationships.Conclusion: The PAI-1 rs1799762 polymorphisms may be associated with the genetic susceptibility of Chinese allergic disease patients with cough performance.

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“…No organic disease (Tamari and Hirota, 2014). Voluntary acceptance of disease-related questionnaires (Haider et al, 2022). No participation in any drug clinical trials within 3 months.…”

Section: Study Design and Participantsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

The 4G/5G polymorphism of plasminogen activator inhibitor type 1 is a predictor of allergic cough

Tang

Lyu²,

Li³

et al. 2023

Front. Genet.

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“…The genetics of asthma is complex, and the functional impacts of known asthma-associated variants are poorly understood ( 6 ). This is possibly due to data conglomeration issues arising from phenotyping complications due to the interaction of asthma with other complex traits.…”

Section: Introductionmentioning

confidence: 99%

De novo identification of complex traits associated with asthma

Zaied,

Fadason,

O’Sullivan

2023

Front. Immunol.

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IntroductionAsthma is a heterogeneous inflammatory disease often associated with other complex phenotypes. Identifying asthma-associated diseases and uncovering the molecular mechanisms mediating their interaction can help detangle the heterogeneity of asthma. Network analysis is a powerful approach for untangling such inter-disease relationships.MethodsHere, we integrated information on physical contacts between common single nucleotide polymorphisms (SNPs) and gene expression with expression quantitative trait loci (eQTL) data from the lung and whole blood to construct two tissue-specific spatial gene regulatory networks (GRN). We then located the asthma GRN (level 0) within each tissue-specific GRN by identifying the genes that are functionally affected by asthma-associated spatial eQTLs. Curated protein interaction partners were subsequently identified up to four edges or levels away from the asthma GRN. The eQTLs spatially regulating genes on levels 0–4 were queried against the GWAS Catalog to identify the traits enriched (hypergeometric test; FDR ≤ 0.05) in each level.ResultsWe identified 80 and 82 traits significantly enriched in the lung and blood GRNs, respectively. All identified traits were previously reported to be comorbid or associated (positively or negatively) with asthma (e.g., depressive symptoms and lung cancer), except 8 traits whose association with asthma is yet to be confirmed (e.g., reticulocyte count). Our analysis additionally pinpoints the variants and genes that link asthma to the identified asthma-associated traits, a subset of which was replicated in a comorbidity analysis using health records of 26,781 asthma patients in New Zealand.DiscussionOur discovery approach identifies enriched traits in the regulatory space proximal to asthma, in the tissue of interest, without a priori selection of the interacting traits. The predictions it makes expand our understanding of possible shared molecular interactions and therapeutic targets for asthma, where no cure is currently available.

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“…Globally, 8–10% of the population suffers from allergic diseases 1 . A complex interplay between environmental and host variables contributes to the development of allergies 2 . The immune deviation towards a Th2 cell type contributes to the pathogenesis of allergies 3,4 .…”

Section: Introductionmentioning

confidence: 99%

“…1 A complex interplay between environmental and host variables contributes to the development of allergies. 2 The immune deviation towards a Th2 cell type contributes to the pathogenesis of allergies. 3,4 The hallmarks of allergic rhinitis include nasal congestion, sneezing, itching, clear rhinorrhoea, and ocular symptoms.…”

mentioning

confidence: 99%

Aberrant expression of suppressor of cytokine signaling (SOCS) molecules contributes to the development of allergic diseases

Jafarzadeh,

Chauhan,

Nemati

et al. 2023

Clin Experimental Allergy

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Suppressor of cytokine signalling (SOCS) proteins bind to certain cytokine receptors, Janus kinases and signalling molecules to regulate signalling pathways, thus controlling immune and inflammatory responses. Dysregulated expression of various types of SOCS molecules was indicated in multiple types of allergic diseases. SOCS1, SOCS2, SOCS3, SOCS5, and cytokine‐inducible SH2 domain protein (CISH) can differentially exert anti‐allergic impacts through different mechanisms, such as suppressing Th2 cell development and activation, reducing eosinophilia, decreasing IgE production, repressing production of pro‐allergic chemokines, promoting Treg cell differentiation and activation, suppressing Th17 cell differentiation and activation, increasing anti‐allergic Th1 responses, inhibiting M2 macrophage polarization, modulating survival and development of mast cells, reducing pro‐allergic activity of keratinocytes, and suppressing pulmonary fibrosis. Although some anti‐allergic effects were attributed to SOCS3, it can perform pro‐allergic impacts through several pathways, such as promoting Th2 cell development and activation, supporting eosinophilia, boosting pro‐allergic activity of eosinophils, increasing IgE production, enhancing the expression of the pro‐allergic chemokine receptor, reducing Treg cell differentiation, increasing pro‐allergic Th9 responses, as well as supporting mucus secretion and collagen deposition. In this review, we discuss the contrasting roles of SOCS proteins in contexts of allergic disorders to provide new insights regarding the pathophysiology of these diseases and possibly explore SOCS proteins as potential therapeutic targets for alleviating allergies.

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Genetics of Asthma and Allergic Diseases

Cited by 8 publications

References 122 publications

The 4G/5G polymorphism of plasminogen activator inhibitor type 1 is a predictor of allergic cough

The 4G/5G polymorphism of plasminogen activator inhibitor type 1 is a predictor of allergic cough

De novo identification of complex traits associated with asthma

Aberrant expression of suppressor of cytokine signaling (SOCS) molecules contributes to the development of allergic diseases

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