The Genetic Factors of the Airway Epithelium Associated with the Pathology of Asthma

Ranjbar, Maral; Whetstone, Christiane E.; Omer, Hafsa; Power, Lucy; Cusack, Ruth; Gauvreau, Gail M.

doi:10.3390/genes13101870

Cited by 16 publications

(7 citation statements)

References 145 publications

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“…However, the manifestation of asthma is not solely dictated by genetic makeup; environmental in uences also play a crucial role. Factors like air pollution and tobacco smoke exposure can exacerbate asthma symptoms, particularly in individuals with genetic susceptibilities (120). This interaction between genetic predispositions and environmental exposures adds complexity to the understanding of asthma heterogeneity, emphasizing the need for comprehensive approaches that consider both genetic and environmental factors in asthma research and healthcare interventions within the EMRO region and beyond.…”

Section: Discussionmentioning

confidence: 99%

Prevalence of Asthma among Children and Adolescents in WHO's Eastern Mediterranean Region: A Meta-Analysis of Over 0.5 Million Participants

Taherian,

Fatemian,

Halimi

et al. 2024

Preprint

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Objective: This study aims to evaluate the epidemiology of asthma among children and adolescents in the Eastern Mediterranean Region (EMRO). Methods: Exhaustive searches were conducted across databases, including PubMed, Scopus, Web of Knowledge Core Collection, Embase, and Google Scholar. The selection criteria included studies in English and Persian languages reporting asthma prevalence in individuals aged 0 to 19 years, using validated questionnaires. Data were extracted and synthesized using the DerSimonian and Laird random effects model. Results: The overall prevalence of asthma in Eastern Mediterranean Regional Office (EMRO) countries, among the 514,468 children and adolescents included in this meta-analysis, was 10.61%, synthesized from 95 studies. Among the countries studied, Qatar exhibited the highest prevalence at 16.69%, followed by Saudi Arabia at 16.57%, Iraq at 16.22%, Oman at 15.20%, and Afghanistan at 14.90%. Adolescents showed a slightly higher prevalence of asthma at 10.10% compared to children at 9.70%. Boys exhibited a higher prevalence at 11.48% compared to girls at 9.75%. Urban areas demonstrated a higher prevalence at 11.27% compared to rural areas at 8.29%. Conclusion: Efforts to reduce asthma prevalence in Arab countries and address underdiagnosis in African nations within the EMRO are crucial. Targeted interventions should focus on addressing environmental triggers and improving access to healthcare. Enhanced diagnostic capabilities and healthcare infrastructure are necessary in African countries. Collaborative action is essential to alleviate the asthma burden and promote respiratory health across the EMRO region.

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Section: Discussionmentioning

confidence: 99%

Prevalence of Asthma among Children and Adolescents in WHO's Eastern Mediterranean Region: A Meta-Analysis of Over 0.5 Million Participants

Taherian,

Fatemian,

Halimi

et al. 2024

Preprint

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“…The epithelial barrier is the first line of defense to external milieu, whose dysfunction is closely linked with inflammatory disorders. Mutations in the genes of vital epithelial barrier proteins are associated with allergic disorders [ 15 , 16 ]. The polymorphisms in the genes of type 2 cytokines (IL-4 and IL-13), alarmins (IL-33 and thymic stromal lymphopoietin [TSLP]), inflammation-related proteins (ADAM33 and HLA), and also vitamin D receptor could either reduce or increase the risk and severity of asthma [ 16 , 17 ].…”

Section: Risk Factors Of Epithelial Barrier Dysfunctionmentioning

confidence: 99%

“…Mutations in the genes of vital epithelial barrier proteins are associated with allergic disorders [ 15 , 16 ]. The polymorphisms in the genes of type 2 cytokines (IL-4 and IL-13), alarmins (IL-33 and thymic stromal lymphopoietin [TSLP]), inflammation-related proteins (ADAM33 and HLA), and also vitamin D receptor could either reduce or increase the risk and severity of asthma [ 16 , 17 ]. In addition, CCL20 , IL6 , IRF4 , MUC5AC , TBX21 , FADS2 , and RUNX1 were reported as asthma-associated genes [ 18 ].…”

Section: Risk Factors Of Epithelial Barrier Dysfunctionmentioning

confidence: 99%

The epithelial barrier theory: Development and exacerbation of allergic and other chronic inflammatory diseases

Küçüksezer

Özdemir

Yazıcı

et al. 2023

Asia Pacific Allergy

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It is now longer than half a century, humans, animals, and nature of the world are under the influence of exposure to many newly introduced noxious substances. These exposures are nowadays pushing the borders to be considered as the causative or exacerbating factors for many chronic disorders including allergic, autoimmune/inflammatory, and metabolic diseases. The epithelial linings serve as the outermost body’s primary physical, chemical, and immunological barriers against external stimuli. The “epithelial barrier theory” hypothesizes that these diseases are aggravated by an ongoing periepithelial inflammation triggered by exposure to a wide range of epithelial barrier–damaging insults that lead to “epithelitis” and the release of alarmins. A leaky epithelial barrier enables the microbiome’s translocation from the periphery to interepithelial and even deeper subepithelial areas together with allergens, toxins, and pollutants. Thereafter, microbial dysbiosis, characterized by colonization of opportunistic pathogen bacteria and loss of the number and biodiversity of commensal bacteria take place. Local inflammation, impaired tissue regeneration, and remodeling characterize the disease. The infiltration of inflammatory cells to affected tissues shows an effort to expulse the tissue invading bacteria, allergens, toxins, and pollutants away from the deep tissues to the surface, representing the “expulsion response.” Cells that migrate to other organs from the inflammatory foci may play roles in the exacerbation of various inflammatory diseases in distant organs. The purpose of this review is to highlight and appraise recent opinions and findings on epithelial physiology and its role in the pathogenesis of chronic diseases in view of the epithelial barrier theory.

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“…An animal disease model mimicking human asthma suggested that approximately 200 genes may contribute to the etiology of asthma ( Temesi et al, 2014 ). Candidate gene studies focusing on biologically relevant genes such as inflammatory and immunological genes and genome-wide association studies (GWAS) have identified a number of genetic susceptibility loci for asthma ( Bonnelykke & Ober, 2016 ; Liu et al, 2022 ; Shen et al, 2017 ; Hsia et al, 2015 ; Garcia-Sanchez et al, 2015 ; Shi, Zhang & Qiu, 2022 ; Ranjbar et al, 2022 ). However, the identified asthma susceptibility loci to date only explain a small portion of the genetic heritability of asthma and additional genetic susceptibility loci to asthma remains to be uncovered.…”

Section: Introductionmentioning

confidence: 99%

Novel genetic variants in long non-coding RNA MEG3 are associated with the risk of asthma

Chiu

Chang

Tsai

et al. 2023

PeerJ

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Background Asthma is the most common chronic inflammatory airway disease worldwide. Asthma is a complex disease whose exact etiologic mechanisms remain elusive; however, it is increasingly evident that genetic factors play essential roles in the development of asthma. The purpose of this study is to identify novel genetic susceptibility loci for asthma in Taiwanese. We selected a well-studied long non-coding RNA (lncRNA), MEG3, which is involved in multiple cellular functions and whose expression has been associated with asthma. We hypothesize that genetic variants in MEG3 may influence the risk of asthma. Methods We genotyped four single nucleotide polymorphisms (SNPs) in MEG3, rs7158663, rs3087918, rs11160608, and rs4081134, in 198 patients with asthma and 453 healthy controls and measured serum MEG3 expression level in a subset of controls. Results The variant AG and AA genotypes of MEG3 rs7158663 were significantly over-represented in the patients compared to the controls (P = 0.0024). In logistic regression analyses, compared with the wild-type GG genotype, the heterozygous variant genotype (AG) was associated with a 1.62-fold [95% confidence interval (CI) [1.18–2.32], P = 0.0093] increased risk and the homozygous variant genotype (AA) conferred a 2.68-fold (95% CI [1.52–4.83], P = 0.003) increased risk of asthma. The allelic test showed the A allele was associated with a 1.63-fold increased risk of asthma (95% CI [1.25–2.07], P = 0.0004). The AG plus AA genotypes were also associated with severe symptoms (P = 0.0148). Furthermore, the AG and AA genotype carriers had lower serum MEG3 expression level than the GG genotype carriers, consistent with the reported downregulation of MEG3 in asthma patients. Conclusion MEG3 SNP rs7158663 is a genetic susceptibility locus for asthma in Taiwanese. Individuals carrying the variant genotypes have lower serum MEG3 level and are at increased risks of asthma and severe symptoms.

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The Genetic Factors of the Airway Epithelium Associated with the Pathology of Asthma

Cited by 16 publications

References 145 publications

Prevalence of Asthma among Children and Adolescents in WHO's Eastern Mediterranean Region: A Meta-Analysis of Over 0.5 Million Participants

Prevalence of Asthma among Children and Adolescents in WHO's Eastern Mediterranean Region: A Meta-Analysis of Over 0.5 Million Participants

The epithelial barrier theory: Development and exacerbation of allergic and other chronic inflammatory diseases

Novel genetic variants in long non-coding RNA MEG3 are associated with the risk of asthma

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