Polymorphisms in the 5‐lipoxygenase activating protein (<i>ALOX5AP</i>) gene are not associated with asthma in an Australian population

Kedda, Mary-Anne; Worsley, Penelope S.; Phelps, Stephanie J.; Duffy, David L.; Thompson, Philip J.

doi:10.1111/j.1365-2222.2005.02188.x

Cited by 9 publications

(6 citation statements)

References 23 publications

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“…Genetic association studies of polymorphisms in ALOX5AP and ALOX5 (16,17) also suggest an influence more specifically on lung function rather than asthma. The association of complement component 3 (C3) expression with airflow obstruction and asthma is consistent with results from several mouse and human studies.…”

Section: Discussionmentioning

confidence: 99%

The Clinical and Environmental Determinants of Airway Transcriptional Profiles in Allergic Asthma

Yang

Tomfohr

Singh

et al. 2012

Am J Respir Crit Care Med

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Rationale: Gene expression profiling of airway epithelial and inflammatory cells can be used to identify genes involved in environmental asthma. Methods: Airway epithelia and inflammatory cells were obtained via bronchial brush and bronchoalveolar lavage (BAL) from 39 subjects comprising three phenotypic groups (nonatopic nonasthmatic, atopic nonasthmatic, and atopic asthmatic) 4 hours after instillation of LPS, house dust mite antigen, and saline in three distinct subsegmental bronchi. RNA transcript levels were assessed using whole genome microarrays. Measurements and Main Results: Baseline (saline exposure) differences in gene expression were related to airflow obstruction in epithelial cells (C3, ALOX5AP, CCL18, and others), and to serum IgE (innate immune genes and focal adhesion pathway) and allergic-asthmatic phenotype (complement genes, histone deacetylases, and GATA1 transcription factor) in inflammatory cells. LPS stimulation resulted in pronounced transcriptional response across all subjects in both airway epithelia and BAL cells, with strong association to nuclear factor-kB and IFNinducible genes as well as signatures of other transcription factors (NRF2, C/EBP, and E2F1) and histone proteins. No distinct transcriptional profile to LPS was observed in the asthma and atopy phenotype. Finally, although no consistent expression changes were observed across all subjects in response to house dust mite antigen stimulation, we observed subtle differences in gene expression (e.g., GATA1 and GATA2) in BAL cells related to the asthma and atopy phenotype. Conclusions: Our results indicate that among individuals with allergic asthma, transcriptional changes in airway epithelia and inflammatory cells are influenced by phenotype as well as environmental exposures.

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Section: Discussionmentioning

confidence: 99%

The Clinical and Environmental Determinants of Airway Transcriptional Profiles in Allergic Asthma

Yang

Tomfohr

Singh

et al. 2012

Am J Respir Crit Care Med

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“…109 Recently, several authors addressed the problem of genetic polymorphism. [110][111][112][113][114] The most comprehensive study of genetic associations with AERD was published by Jinnai et al 106 Using 370 SNPs from 63 candidate genes, almost 200 patients with AERD were compared with aspirin-tolerant asthmatic subjects and control subjects. A gene coding for EP receptor 2 was the only one significantly associated with AERD.…”

Section: Pathogenesismentioning

confidence: 99%

Clinical and pathologic perspectives on aspirin sensitivity and asthma

Stevenson

Szczeklik

2006

Journal of Allergy and Clinical Immunology

291

258

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Aspirin and other nonsteroidal anti-inflammatory drugs that inhibit COX-1 induce unique nonallergic reactions, consisting of attacks of rhinitis and asthma. These hypersensitivity reactions occur in a subset of asthmatic subjects, thus identifying them as having this exclusive clinical presentation. We refer to these patients as having aspirin-exacerbated respiratory disease, a disease process that produces devastating eosinophilic inflammation of both the upper and lower respiratory tracts. This review focuses on a description of patients with aspirin-exacerbated respiratory disease, methods available to diagnose their condition, the unique ability of all nonsteroidal anti-inflammatory drugs that inhibit COX-1 to cross-react with aspirin, an update on pathogenesis, and current thoughts about treatment.

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“…Certain FLAP haplotypes were also linked to risks of myocardial infarction (MI) and stroke in individuals from the Iceland and the UK [76]. The association of the FLAP gene with stroke was replicated in Scottish, central European, Australian and Japanese populations, although such linkage was not validated in a North American subpopulation [77][78][79][80][81]. In addition, Cippolone and coworkers have reported a potential association between 5-LO expression and plaque instability in patients with complicated carotid plaques [82].…”

Section: -Lo/flap-lt Cascade In Cvdmentioning

confidence: 94%

Lipoxygenase and prostaglandin G/H synthase cascades in cardiovascular disease

Zhao¹,

Großer²,

Fries³

et al. 2006

Expert Review of Clinical Immunology

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The 12/15-lipoxygenase (LO) cascade governs the generation of 12-hydroperoxy-eicosatetraenoic acid (HPETE) and 15-HPETE from arachidonic acid. The 5-LO pathway plays a fundamental role in the biosynthesis of leukotrienes, essential inflammatory lipid mediators. Cyclooxygenase (COX)-1 and -2 biosynthetic pathways are responsible for prostaglandin and thromboxane formation. Experimental investigations in animal models using 12/15-LO deficient mice, 12/15-LO or 15-LO transgenic mice, or pharmacological 15-LO inhibition have all demonstrated the essential role of 12/15-LO in atherogenesis. The underlying mechanisms are linked to low-density lipoprotein oxidation, pro-inflammatory Th1 cytokine production and enhanced monocyte-endothelial cell interaction. Human genetic studies as well as disruption of the 5-LO gene in mouse models of hyperlipidemia revealed that 5-LO and 5-LO-activating protein are associated with risks of human cardiovascular disease, and that this cascade plays an important role in aortic aneurysm pathogenesis through leukotriene-mediated inflammatory chemokine production. COX-1 plays an active role in atherogenesis via thromboxane A(2), while COX-2-derived prostaglandin (PGI(2)) protects against atherosclerosis in murine models. Recent data demonstrated that selective inhibition of COX-2 augments the risk of cardiovascular events in patients. Selective inhibition or blockade of selective components in these two enzymatic pathways through systemic drug delivery or medical device approaches (e.g., drug-eluting stents) may have therapeutic benefit against certain cardiovascular diseases.

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Polymorphisms in the 5‐lipoxygenase activating protein (ALOX5AP) gene are not associated with asthma in an Australian population

Abstract: These findings in a large, well characterized asthma population, reveal that, while FLAP is an important enzyme in cys-LTs biosynthesis, polymorphisms in the ALOX5AP gene are not likely to be functionally associated with the asthma phenotype.

Cited by 9 publications

References 23 publications

The Clinical and Environmental Determinants of Airway Transcriptional Profiles in Allergic Asthma

The Clinical and Environmental Determinants of Airway Transcriptional Profiles in Allergic Asthma

Clinical and pathologic perspectives on aspirin sensitivity and asthma

Lipoxygenase and prostaglandin G/H synthase cascades in cardiovascular disease

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