Association between Polymorphisms in Bitter Taste Receptor Genes and Clinical Features in Korean Asthmatics

Yoon, Sun‐Young; Shin, Eun-Soon; Park, So Young; Kim, Sujeong; Kwon, Hyouk‐Soo; Cho, You Sook; Moon, Hee‐Bom; Kim, Tae‐Bum

doi:10.1159/000443796

Cited by 15 publications

(12 citation statements)

References 51 publications

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“…We also need to carefully assess the therapy effect of bitter tastants for different individuals, considering there may be big differences in genetic expression types and abundance of TAS2Rs from person to person (Yoon et al, 2016). It is also well known that children are more sensitive to bitter tastants than adults (Mennella et al, 2014).…”

Section: Discussion and Future Directionsmentioning

confidence: 99%

Toward the Identification of Extra-Oral TAS2R Agonists as Drug Agents for Muscle Relaxation Therapies via Bioinformatics-Aided Screening of Bitter Compounds in Traditional Chinese Medicine

Luo

Jin

et al. 2019

Front. Physiol.

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Significant advances have been made in the past decade in mapping the distributions and the physiological functions of extra-oral bitter taste receptors (TAS2Rs) in nongustatory tissues. In particular, it has been found that TAS2Rs are expressed in various muscle tissues and activation of TAS2Rs can lead to muscle cell relaxation, which suggests that TAS2Rs may be important new targets in muscle relaxation therapy for various muscle-related diseases. So far, however, there is a lack of potent extra-oral TAS2R agonists that can be used as novel drug agents in muscle relaxation therapies. Interestingly, traditional Chinese medicine (TCM) often characterizes a drug's property in terms of five distinct flavors (bitter, sweet, sour, salty, and pungent) according to its taste and function, and commonly regards "bitterness" as an intrinsic property of "good medicine." In addition, many bitter flavored TCM are known in practice to cause muscle relaxation after long term use, and in lab experiments the compounds identified from some bitter flavored TCM do activate TAS2Rs and thus relax muscle cells. Therefore, it is highly possible to discover very useful extra-oral TAS2R agonists for muscle relaxation therapies among the abundant bitter compounds used in bitter flavored TCM. With this perspective, we reviewed in literature the distribution of TAS2Rs in different muscle systems with a focus on the map of bitter flavored TCM which can regulate muscle contractility and related functional chemical components. We also reviewed the recently established databases of TCM chemical components and the bioinformatics software which can be used for high-throughput screening and data mining of the chemical components associated with bitter flavored TCM. All together, we aim to present a knowledge-based approach and technological platform for identification or discovery of extra-oral TAS2R agonists that can be used as novel drug agents for muscle relaxation therapies through screening and evaluation of chemical compounds used in bitter flavored TCM.

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Section: Discussion and Future Directionsmentioning

confidence: 99%

Toward the Identification of Extra-Oral TAS2R Agonists as Drug Agents for Muscle Relaxation Therapies via Bioinformatics-Aided Screening of Bitter Compounds in Traditional Chinese Medicine

Luo

Jin

et al. 2019

Front. Physiol.

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“…They are also related to disease outcomes (asthma control, CRS severity) and display significant heterogeneity, which affects their function. For example, genetic variations were associated with lower asthma control and better bronchodilator response (91). T2R38 genetic polymorphism predisposes to infection in upper airways via decreased NO production from epithelial cells in response to bacterial products (84).…”

Section: Figure 2 the Dynamic And Complex Interaction Between Risk Fmentioning

confidence: 99%

Precision medicine and phenotypes, endotypes, genotypes, regiotypes, and theratypes of allergic diseases

Agache

Akdiş

2019

Journal of Clinical Investigation

228

184

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in which microRNAs (miRNAs) play a central role (Table 3). High-throughput profiling studies of well-characterized patients, including analyses of gene expression (e.g., microarrays and RNA sequencing transcriptomics), can help to identify combined signatures for type 2 and non-type 2 endotypes. They are enriching the available data for the identification of new potential targets. As critical components in the regulation of tissue homeostasis, miRNAs represent a very attractive field of precision medicine research in asthma and allergic diseases, as they have been linked to many biological mechanisms underlying Th2 cell and macrophage polarization, regulation of ILC2 biology, steroidresistant asthma phenotype, airway smooth muscle dysfunction, and impaired antiviral innate immunity (Table 3 and refs. 15-25). Thus, miRNAs represent a modifiable downstream target that will expand the precision medicine approach beyond the type 2/ non-type 2 paradigm. In one notable example of this approach, the use of gene expression microarrays on bronchial epithelial cells obtained from patients with asthma led to the identification of periostin, an IL-13-responsive biomarker (26-30). However, expression signatures are not highly specific for type 2 asthma: a recent study showed type 2 airway gene expression in a subset of patients with chronic obstructive pulmonary disease (COPD) (31).

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“…The extent to which polymorphisms of individual TAS2Rs impact the functionality of cells associated with the respiratory system is poorly understood. Polymorphisms in TAS2Rs have been linked to chronic rhinosinusitis (CRS), which is an inflammatory disorder of the nose and paranasal sinuses and in asthma (Adappa et al, 2013; Gallo et al, 2016; Yoon et al, 2016). Some have shown that the rs10246939 SNP ( TAS2R38 nucleotide 296 to valine) and other TAS2R polymorphisms are associated with CRS (Adappa et al, 2013; Mfuna et al, 2014; Cohen, 2017).…”

Section: Receptor Polymorphisms Disease Association and Development mentioning

confidence: 99%

“…However, others have demonstrated a lack of an association of haplotypes between CRS patients, either with (CRSwNP) or without (CRSsNP) nasal polyps, (Gallo et al, 2016). However, at least one study strongly supports identification of polymorphisms in TAS2Rs as possible genetic markers to predict outcomes in asthma (Yoon et al, 2016). Although these association studies have identified a possible link between TAS2R polymorphisms and respiratory diseases, a causal link is yet to be established and the specific contribution toward physiological process remains to be defined.…”

Section: Receptor Polymorphisms Disease Association and Development mentioning

confidence: 99%

Bitter Taste Receptors for Asthma Therapeutics

et al. 2019

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Clinical management of asthma and chronic obstructive pulmonary disease (COPD) has primarily relied on the use of beta 2 adrenergic receptor agonists (bronchodilators) and corticosteroids, and more recently, monoclonal antibody therapies (biologics) targeting specific cytokines and their functions. Although these approaches provide relief from exacerbations, questions remain on their long-term efficacy and safety. Furthermore, current therapeutics do not address progressive airway remodeling (AR), a key pathological feature of severe obstructive lung disease. Strikingly, agonists of the bitter taste receptors (TAS2Rs) deliver robust bronchodilation, curtail allergen-induced inflammatory responses in the airways and regulate airway smooth muscle (ASM) cell proliferation and mitigate features of AR in vitro and in animal models. The scope of this review is to provide a comprehensive and systematic insight into our current understanding of TAS2Rs with an emphasis on the molecular events that ensue TAS2R activation in distinct airway cell types and expand on the pleiotropic effects of TAS2R targeting in mitigating various pathological features of obstructive lung diseases. Finally, we will discuss specific opportunities that could help the development of selective agonists for specific TAS2R subtypes in the treatment of asthma.

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Association between Polymorphisms in Bitter Taste Receptor Genes and Clinical Features in Korean Asthmatics

Cited by 15 publications

References 51 publications

Toward the Identification of Extra-Oral TAS2R Agonists as Drug Agents for Muscle Relaxation Therapies via Bioinformatics-Aided Screening of Bitter Compounds in Traditional Chinese Medicine

Toward the Identification of Extra-Oral TAS2R Agonists as Drug Agents for Muscle Relaxation Therapies via Bioinformatics-Aided Screening of Bitter Compounds in Traditional Chinese Medicine

Precision medicine and phenotypes, endotypes, genotypes, regiotypes, and theratypes of allergic diseases

Bitter Taste Receptors for Asthma Therapeutics

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