Cysteinyl Leukotrienes Pathway Genes, Atopic Asthma and Drug Response: From Population Isolates to Large Genome-Wide Association Studies.

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Cysteinyl Leukotrienes Pathway Genes, Atopic Asthma and Drug Response: From Population Isolates to Large Genome-Wide Association Studies.

Front Pharmacol. 2016;7:299

Authors: Thompson MD, Capra V, Clunes MT, Rovati GE, Stankova J, Maj MC, Duffy DL

Abstract
Genetic variants associated with asthma pathogenesis and altered response to drug therapy are discussed. Many studies implicate polymorphisms in genes encoding the enzymes responsible for leukotriene synthesis and intracellular signaling through activation of seven transmembrane domain receptors, such as the cysteinyl leukotriene 1 (CYSLTR1) and 2 (CYSLTR2) receptors. The leukotrienes are polyunsaturated lipoxygenated eicosatetraenoic acids that exhibit a wide range of pharmacological and physiological actions. Of the three enzymes involved in the formation of the leukotrienes, arachidonate 5 lipoxygenase 5 (ALOX5), leukotriene C4 synthase (LTC4S), and leukotriene hydrolase (LTA4H) are all polymorphic. These polymorphisms often result in variable production of the CysLTs (LTC4, LTD4, and LTE4) and LTB4. Variable number tandem repeat sequences located in the Sp1-binding motif within the promotor region of the ALOX5 gene are associated with leukotriene burden and bronchoconstriction independent of asthma risk. A 444A > C SNP polymorphism in the LTC4S gene, encoding an enzyme required for the formation of a glutathione adduct at the C-6 position of the arachidonic acid backbone, is associated with severe asthma and altered response to the CYSLTR1 receptor antagonist zafirlukast. Genetic variability in the CysLT pathway may contribute additively or synergistically to altered drug responses. The 601 A > G variant of the CYSLTR2 gene, encoding the Met201Val CYSLTR2 receptor variant, is associated with atopic asthma in the general European population, where it is present at a frequency of ?2.6%. The variant was originally found in the founder population of Tristan da Cunha, a remote island in the South Atlantic, in which the prevalence of atopy is approximately 45% and the prevalence of asthma is 36%. In vitro work showed that the atopy-associated Met201Val variant was inactivating with respect to ligand binding, Ca(2+) flux and inositol phosphate generation. In addition, the CYSLTR1 gene, located at Xq13-21.1, has been associated with atopic asthma. The activating Gly300Ser CYSLTR1 variant is discussed. In addition to genetic loci, risk for asthma may be influenced by environmental factors such as smoking. The contribution of CysLT pathway gene sequence variants to atopic asthma is discussed in the context of other genes and environmental influences known to influence asthma.

PMID: 27990118 [PubMed – in process]

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Keeping asthma symptoms in check could prevent large number of deaths, study … – Radio Australia


Radio Australia

Keeping asthma symptoms in check could prevent large number of deaths, study
Radio Australia
The first national snapshot of asthma control has found a significant number of deaths could be prevented if sufferers kept their symptoms in check. The Australian study found almost half of all adult asthma sufferers had poor control over their
Aussies need more asthma symptom controlEchonetdaily

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Keeping asthma symptoms in check could prevent large number of deaths, study … – ABC Online


ABC Online

Keeping asthma symptoms in check could prevent large number of deaths, study
ABC Online
The first national snapshot of asthma control has found a significant number of deaths could be prevented if sufferers kept their symptoms in check. The Australian study found almost half of all adult asthma sufferers had poor control over their
Aussies need more asthma symptom controlNEWS.com.au

all 6 news articles »

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Large CDC survey detects drop in asthma rates, but researchers cautious about … – Minneapolis Star Tribune


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Large CDC survey detects drop in asthma rates, but researchers cautious about
Minneapolis Star Tribune
NEW YORK — A new survey suggests asthma in the U.S. may finally be on the decline. But the results are so surprising that health officials are cautious about claiming a downturn. "I wouldn't say it's good news — yet," said the study's lead author
Study Suggest Asthma Is On The Decline, Doctors Are CautiousABC6OnYourSide.com

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Temporal Asthma Patterns Using Repeated Questionnaires over 13 Years in a Large French Cohort of Women.

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Temporal Asthma Patterns Using Repeated Questionnaires over 13 Years in a Large French Cohort of Women.

PLoS One. 2013;8(5):e65090

Authors: Sanchez M, Bousquet J, Le Moual N, Jacquemin B, Clavel-Chapelon F, Humbert M, Kauffmann F, Tubert-Bitter P, Varraso R

Abstract
Variable expression is one aspect of the heterogeneity of asthma. We aimed to define a variable pattern, which is relevant in general health epidemiological cohorts. Our objectives were to assess whether: 1) asthma patterns defined using simple asthma questions through repeated measurements could reflect disease variability 2) these patterns may further be classified according to asthma severity/control. Among 70,428 French women, we used seven questionnaires (1992-2005) and a comprehensive reimbursement database (2004-2009) to define three reliable asthma patterns based on repeated positive answers to the ever asthma attack question: “never asthma” (n?=?64,061); “inconsistent” (“yes” followed by “no”, n?=?3,514); “consistent” (fully consistent positive answers, n?=?2,853). The “Inconsistent” pattern was related to both long-term (childhood-onset asthma with remission in adulthood) and short-term (reported asthma attack in the last 12 months, associated with asthma medication) asthma variability, showing that repeated questions are relevant markers of the variable expression of asthma. Furthermore, in this pattern, the number of positive responses (1992-2005) predicted asthma drug consumption in subsequent years, a marker of disease severity. The “Inconsistent” pattern is a phenotype that may capture the variable expression of asthma. Repeated answers, even to a simple question, are too often neglected.

PMID: 23741466 [PubMed – in process]

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New online resource for information on large and small airway inflammation in … – Southgate News Herald

New online resource for information on large and small airway inflammation in
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The Asthma and Allergy Foundation of America and Teva Respiratory announced today the launch of Get Smart About Asthma, a comprehensive online asthma management resource that takes a look at the underlying cause of asthma – inflammation.
O2 Media's Designing Spaces™ Show on Lifetime TV to “Get Smart About PR.com (press release)

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New online resource for information on large and small airway inflammation in … – Heritage Newspapers

New online resource for information on large and small airway inflammation in
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The Asthma and Allergy Foundation of America and Teva Respiratory announced today the launch of Get Smart About Asthma, a comprehensive online asthma management resource that takes a look at the underlying cause of asthma – inflammation.
O2 Media's Designing Spaces™ Show on Lifetime TV to “Get Smart About PR.com (press release)

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New online resource for information on large and small airway inflammation in … – Dearborn Press and Guide

New online resource for information on large and small airway inflammation in
Dearborn Press and Guide
The Asthma and Allergy Foundation of America and Teva Respiratory announced today the launch of Get Smart About Asthma, a comprehensive online asthma management resource that takes a look at the underlying cause of asthma – inflammation.
O2 Media's Designing Spaces™ Show on Lifetime TV to “Get Smart About PR.com (press release)

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Weather warning for asthma sufferers as large dust storm to sweep across UAE – The National

Weather warning for asthma sufferers as large dust storm to sweep across UAE
The National
DUBAI // A large dust storm will be kicked up by high winds this weekend and the weather bureau has advised those with asthma or other dust allergies to stay indoors tomorrow. The weekend will also see rain over some parts of the UAE. “Winds at a speed
Rain and dusty winds expected during the weekendgulfnews.com

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Hay Fever and Asthma as Markers of Atopic Immune Response and Risk of Colorectal Cancer in Three Large Cohort Studies.

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Hay Fever and Asthma as Markers of Atopic Immune Response and Risk of Colorectal Cancer in Three Large Cohort Studies.

Cancer Epidemiol Biomarkers Prev. 2013 Mar 19;

Authors: Jacobs EJ, Gapstur SM, Newton CC, Turner MC, Campbell PT

Abstract
BACKGROUND: In a previous analysis of 12 cancers in the Cancer Prevention Study II (CPS-II) cohort including follow-up from 1982-2000, having both hay fever and asthma was associated with lower colorectal cancer mortality. The combination of these allergic conditions may be a marker for allergy-related immune responses that could inhibit colorectal carcinogenesis.METHODS: We examined the association of having both hay fever and asthma with colorectal cancer mortality among 1,023,191 participants in CPS-I, followed from 1959-1972, and 1,102,092 participants in CPS-II, now followed from 1982-2008. We also examined associations with colorectal cancer incidence among 174,917 participants in the CPS-II Nutrition Cohort, a subgroup of CPS-II followed from 1992-2007. During the follow-up, there were 5,644 colorectal cancer deaths in CPS-I, 13,558 colorectal cancer deaths in CPS-II, and 3,365 incident colorectal cancer cases in the CPS-II Nutrition Cohort. Cox proportional hazards regression was used to calculate multivariable-adjusted relative risks (RR) and 95% confidence intervals (CI).RESULTS: RRs for colorectal cancer mortality associated with having both asthma and hay fever, compared with neither condition, were 0.90 (95% CI, 0.74-1.09) in CPS-I, 0.79 (95% CI, 0.69-0.91) in CPS-II, and 0.83 (95% CI, 0.74-0.92) when results from both cohorts were combined in a meta-analysis. The corresponding RR for colorectal cancer incidence in the CPS-II Nutrition Cohort was 0.90 (95% CI, 0.71-1.14).CONCLUSION: These results support an association between having both hay fever and asthma and modestly lower colorectal cancer mortality.Impact: Research examining other potential markers of allergy-related immune response in relation to colorectal cancer is warranted. Cancer Epidemiol Biomarkers Prev; 22(4); 1-9. ©2013 AACR.

PMID: 23513040 [PubMed – as supplied by publisher]

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