Profound Overexpression of Leukotriene C&lt;sub&gt;4&lt;/sub&gt; Synthase in Bronchial Biopsies from Aspirin-Intolerant Asthmatic Patients

Sampson, Anthony P.; Cowburn, Andrew S.; Sładek, Krzysztof; Adamek, Lukasz; Nizankowska, E; Szczeklik, A; Lam, Bing; Penrose, John F.; Austen, K. Frank; Holgate, Stephen T.

doi:10.1159/000237600

Cited by 97 publications

(72 citation statements)

References 3 publications

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“…Specifically, a study in a Korean population, showed that the negative regulation of leukotriene C4 synthase (LTC4S) by thromboxane A2 receptor (TBXA2) being modulated by the TBXA2R+795T>C polymorphism, augmented bronchoconstrictive response to acetyl salicylic acid (ASA), which can contribute to AIA susceptibility (Kim et al, 2005). It has also been known that overproduction of cys-leukotrienes (cysLTs) in bronchial epithelium and inhibition of prostaglandin synthesis by cyclooxygenase (COX) inhibition underlie the development of AIA (Sampson et al, 1997;Pierzchalska et al, 2000;Antczak et al, 2002). However, in contrast to that, a recent study showed that LTC4S and cysteinyl leukotriene receptor 1 (CYSLTR1) gene polymorphisms were not associated with AIA occurrence in a study involving Korean individuals (Choi et al, 2004).…”

Section: Discussionmentioning

confidence: 99%

Association of SLC6A12 variants with aspirin‐intolerant asthma in a Korean population

Pasaje

Kim

Park

et al. 2010

Annals of Human Genetics

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SummaryAspirin-intolerant asthma (AIA) occurs from asthma exacerbation after exposure to aspirin. However, the underlying mechanisms of AIA occurrence are still unclear. The critical role of the solute carrier family 6 (neurotransmitter transporter, betaine/GABA) member 12 (SLC6A12) gene in GABAergic transmission, which is associated with mucus production in asthma, makes it a candidate gene for AIA association study. Eight single nucleotide polymorphisms (SNPs) in SLC6A12 were genotyped in 163 aspirin-intolerant asthma (AIA) and 429 aspirin-tolerant asthma (ATA) patients of Korean ethnicity. Associations between polymorphisms of SLC6A12 and AIA were analysed using multivariate logistic analysis. Results showed that two polymorphisms and a haplotype in SLC6A12, rs499368 (P = 0.005; P corr = 0.03), rs557881 (nonsynonymous C10R, P = 0.007; P corr = 0.04), and SLC6A12_BL1_ht1 (P = 0.009; P corr = 0.05) respectively, were significantly associated with AIA after multiple testing corrections. In addition, SNPs of SLC6A12 were significantly associated with the fall rate of FEV 1 by aspirin provocation suggesting that SLC6A12 could affect reversibility of lung function abnormalities in AIA patients. Although these results are preliminary and future replications are needed to confirm these findings, this study showed evidence of association between variants in SLC6A12 and AIA occurrence among asthmatics in a Korean population.

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Section: Discussionmentioning

confidence: 99%

Association of SLC6A12 variants with aspirin‐intolerant asthma in a Korean population

Pasaje

Kim

Park

et al. 2010

Annals of Human Genetics

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“…Up-regulation of these enzymes is observed in the lungs, sinuses, and nasal polyps of AERD subjects, localized in large part to the infiltrating eosinophils, and resident mast cells. 12,15,21,22 AERD subjects also demonstrate an increased sensitivity to CysLTs, 23 reflecting in part their up-regulation of CysLT 1 receptors. 24 The two originally characterized CysLT receptors were distinguished by their differing potency for the CysLTs: CysLT1 receptors primarily respond to LTD 4 , whereas CysLT2 receptors respond equally to LTD 4 and LTC 4 .…”

Section: Cysteinyl Leukotriene Overproduction and Overresponsiveness mentioning

confidence: 99%

Factors Driving the Aspirin Exacerbated Respiratory Disease Phenotype

Steinke

Borish

2015

Am J Rhinol�Allergy

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“…An interesting group of subjects are those with aspirin-sensitive asthma, in that one might predict that genetic variability in LT pathways might well predict aspirin sensitivity [23]. Perhaps surprisingly, no single genetic variant has yet been identified that explains aspirin sensitivity or response to cysteinyl LT receptor antagonists in these pathways.…”

Section: Leukotriene C 4 Synthasementioning

confidence: 99%

Pharmacogenetics and asthma: false hope or new dawn?

Hall¹,

Sayers²

2007

European Respiratory Journal

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Pharmacogenetic approaches provide the opportunity to improve prescribing for asthmatic patients in order to optimise efficacy and prevent side-effects. Currently, there are comprehensive data available on the extent of genetic variation in the human genome that will further this area of research. However, less is known about the functional consequences of many of the identified polymorphisms in genes whose products may predict drug efficacy. In addition, there is a shortage of well-designed, adequately powered clinical studies in this area. This series summarises the current state of knowledge and identifies areas for further research.

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Profound Overexpression of Leukotriene C<sub>4</sub> Synthase in Bronchial Biopsies from Aspirin-Intolerant Asthmatic Patients

Cited by 97 publications

References 3 publications

Association of SLC6A12 variants with aspirin‐intolerant asthma in a Korean population

Association of SLC6A12 variants with aspirin‐intolerant asthma in a Korean population

Factors Driving the Aspirin Exacerbated Respiratory Disease Phenotype

Pharmacogenetics and asthma: false hope or new dawn?

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