Bronchial Nitric Oxide Flux May Be Better Associated with Inducible Nitric Oxide Synthase Promoter Methylation

Journal of Allergy and Clinical Immunology

Lozupone

Schwartz

2017

132

Asthma prevalence has been on the increase, especially in North America compared to other continents. However, the prevalence of asthma differs worldwide and in many countries the prevalence of asthma is stable or decreasing. This highlights the influence of environmental exposures, such as allergens, air pollution, and environmental microbiome, on disease etiology and pathogenesis. The epigenome may provide the unifying mechanism that translates the influence of environmental exposures to changes in gene expression, respiratory epithelial function, and immune cell skewing that are hallmarks of asthma. In this review, we will introduce the concept of the environmental epigenome in asthma, summarize previous publications of relevance to this field, and discuss future directions.

Section: Asthma Epigeneticsmentioning

confidence: 99%

The environment, epigenome, and asthma

Journal of Allergy and Clinical Immunology

Lozupone

Schwartz

2017

132

“…While animal studies have begun to decipher the role of epigenetic regulation of gene expression associated with the development of allergic airway disease in the lung, several recent publications in human cohorts have examined DNA methylation in cells outside of the lung: peripheral blood [62], buccal cells [63,64] and nasal cells [65]. These early studies have only demonstrated statistical association of DNA methylation and specific exposure or asthma phenotype, but have not elucidated the role of DNA methylation in the control of gene expression in human asthma.…”

Section: Dna Methylation and Asthma: Human Studiesmentioning

confidence: 99%

“…BRETON et al [63] demonstrated that DNA methylation in promoters of two arginase genes (Arg1 and Arg2) is associated with exhaled NO in children with asthma from the Children's Health Study and indicates a role for epigenetic regulation of nitric oxide production. In a pilot study in the Columbia Center for Children's Environmental Health cohort, KURIAKOSE et al [64] found that iNOS methylation was not significantly associated with exhaled NO fraction (FeNO), but was inversely associated with bronchial NO flux. This latter study emphasises the importance of careful selection of clinical parameters used in the association study.…”

Section: Dna Methylation and Asthma: Human Studiesmentioning

confidence: 99%

Epigenetics and prenatal influences on asthma and allergic airways disease

2014

Breathe

Epigenetics and prenatal influences on asthma and allergic airways disease IntroductionAsthma is a complex, heritable disease that has been increasing in prevalence, incidence and severity [1], although recent evidence suggests that the prevalence of asthma and allergies may have come to a plateau in developed countries [2]. Several separate lines of evidence support a role for epigenetics in asthma. First, asthma, like epigenetic mechanisms, is heritable. While asthma is a strongly familial condition (36-79% heritability) with a non-Mendelian pattern of inheritance and polymorphisms in more than 100 genes [3-6], these associations have infrequently been replicated and genetics has explained only a small portion of the aetiology of this disease [4]. Second, asthma, like epigenetic mechanisms, shows a parentof-origin transmission of inheritance with an affected mother significantly more likely to transmit the disease than an affected father [7]. These parent-of-origin effects may result from immune interactions between the fetus and the mother [8]. Alternatively, the maternal effect may be the result of epigenetically regulated genomic imprinting [9]. Several known genes show parent-of-origin effects on allergic disease; these genes include the FceRI-b locus [10], and the Spink5 gene [11]. Third, asthma, like epigenetic mechanisms [12,13], is affected by in utero exposures HERMES syllabus link: modules A.1, B.6 Statement of InterestNone declared.

“…While animal studies have begun to decipher the role of epigenetic regulation of gene expression associated with the development of allergic airway disease in the lung, several recent publications in human cohorts have examined DNA methylation in cells outside of the lung - peripheral blood 136 , buccal cells 137, 138 and nasal cells 139 . These early studies have only demonstrated statistical association of DNA methylation and specific exposure or asthma phenotype but have not elucidated the role of DNA methylation in the control of gene expression in human asthma.…”

Section: Asthma Epigenetics – Human Studiesmentioning

confidence: 99%

“…Breton et al demonstrated that DNA methylation in promoters of two arginase genes (Arg1 and Arg2) is associated with exhaled nitric oxide in children with asthma from the Children’s Health Study and indicates a role for epigenetic regulation of nitric oxide production 137 . In a pilot study in the Columbia Center for Children’s Environmental Health cohort, Kuriakose and coworkers found that iNOS methylation was not significantly associated with fraction exhaled NO (Fe NO ) but was associated inversely with J NO (bronchial NO flux) 138 . This latter study emphasizes the importance of careful selection of clinical parameters used in the association study.…”

Section: Asthma Epigenetics – Human Studiesmentioning

confidence: 99%

Epigenetic mechanisms and the development of asthma

Journal of Allergy and Clinical Immunology

Schwartz

2012

118

Asthma is heritable, influenced by the environment, and is modified by in utero exposures and aging; all of these features are also common to epigenetic regulation. Furthermore, the transcription factors that are involved in the development of mature T cells that are critical to the Th2 immune phenotype in asthma are regulated by epigenetic mechanisms. Epigenetic marks - DNA methylation, modifications of histone tails, and non-coding RNAs – work in concert with other components of cellular regulatory machinery to control spatial and temporal level of expressed genes. Technology to measure epigenetic marks on genomic scale and comprehensive approaches to data analysis have recently emerged and continue to improve. Alterations in epigenetic marks have been associated with exposures relevant to asthma, particularly air pollution and tobacco smoke, as well as asthma phenotypes in a few population-based studies. On the other hand, animal studies have begun to decipher the role of epigenetic regulation of gene expression associated with the development of allergic airway disease. Epigenetic mechanisms represent a promising line of inquiry that may, in part, explain the inheritance and immunobiology of asthma.